Background: Since the 1970s, Thailand has recognized the irrational use of medicine in both public and private healthcare delivery, as well as in self-medication from unreliable sources. Various governments have attempted to address this issue. During the last decade, the Rational Drug Use (RDU) hospital policy was systematically implemented nationwide; however, RDU remains a big challenge. With no paucity, Thailand is moving forward with the "RDU Country" policy for the next decade. The goals of this policy are to make RDU as a social norm, a basic right, and a quality of healthcare service in Thailand. Purposes: To develop a mechanism for implementing the "RDU Country" policy and to create a model for achieving it by focusing on a health systems approach, monitoring and evaluation, and developing mechanisms for cooperation in the development of national indicators. This includes studying the form and structure of the central agency responsible for rational drug use (the RDU Center) and analyzing its working mechanism with the concept of political economy. Methods: A 4 steps with 1- cycle of action research was employed to gather data using qualitative methods. The principal investigators, who are embedded as practitioners within the central government agency responsible for promoting rational drug use, collected the data between May 2021 and October 2022. The development of mechanisms for implementing national policies on rational drug use using an integrated theoretical framework to put policy into practice. The action research began with a review of the problem situation, past actions, set goals, operational definitions, principles, and guidelines were established for implementing the "RDU Country" policy, and plans were made to put these guidelines into practice at both the central and regional levels. At the central level, this was achieved through the efforts of the Sub-Committee for the Promotion of Rational Use of Drugs and related working groups, using the concept of a triangle that moves mountains. At the regional level, the development of a "Rational Drug Use Province" (RDU Province) was proposed as a policy package. The goal of an "RDU Province" is to enhance the quality of services to promote rational drug use in both public and private sectors and to solve drug problems in the community sustainably through the development of mechanisms at the provincial level. This would involve achieving propulsion in each district through the participation of all sectors, in line with the concept of developing a district health system using the six-building block health system development concept according to the guidelines of the World Health Organization. This is also relevant to the development of healthy communities to make rational drug use a new social norm. There were four research areas distributed in each region with different contexts. Lessons were learned from operations in these areas, and observations and evaluations were conducted to provide feedback to the research areas. Results: The development of systems and mechanisms for implementing the country's policy on rational drug use and monitoring its implementation requires a system governance mechanism for effective policy implementation at both the central and regional levels. This relies on an efficient mechanism among policy makers, policy actors, and those affected by the policy. There is a mechanism for the central agency responsible for rational drug use (the RDU center), which is a sub-government mechanism that acts as a "connection" between policy makers and practitioners. In addition, provincial and district agencies have a coordinator or responsible person (the RDU coordinator) with appropriate capacity in terms of both leadership and technical competency. An important leverage point for the development of an "RDU Province" is the presence of policy actors at the local level who need direction and support from executives at both the provincial and regional levels. One of the policy actors responsible for promoting rational drug use (RDU coordinator) at the provincial and district levels must be competent in collaboration with the stakeholders. Developing RDU Province faced several significant challenges such as the cooperation with private healthcare settings, limited understanding of healthcare practitioners and health workers about rational drug use literacy, and RDU information systems in hospitals and communities. Furthermore, a study and development of the implementation model of an RDU Center under the structure of the National Drug Policy Division of the Food and Drug Administration is necessary to enable it to perform its role as the resolution of the National Drug System Development Committee. This includes the development of mechanisms to drive policy implementation in both central and regional areas, as well as the development of monitoring and evaluation systems and information systems for monitoring and evaluation in collaboration with related agencies. This is being driven by a "superstructure” with bureaucracy that represents the power of the state, using the concept of “a triangle that moves the mountain” and extending the work system between government agencies using the concept of political economy with 3 main mechanisms as follows: firstly, health care service quality supervision through professional councils, quality system mechanisms, regulatory mechanisms from the ministry that oversees public health facilities, and legal mechanisms; secondly, a mechanism for regulatory activities of pharmaceutical manufacturers/companies through law; and thirdly, a financial mechanism through the government health insurance fund, which is the positive reinforcement. However, the RDU Center also needs to make decisions and seriously take action on proper management of structures and roles under the mission of the Food and Drug Administration, including both its consumer protection role for health products and its mission as a government agency at the department level in implementing national drug policy to routine work system. Conclusion: An important and challenging issue for Thailand's health system in achieving rational drug use, which have been persisting for more than four decades, is finding a solution to drug problems in the community. Therefore, the design of the superstructure of the health system is required to provide alternative access to basic essential medicines from reliable drug distribution sources for people in all districts, regardless of differences in education, income, or area of residence. People should have access to necessary and reliable information to make informed decisions about their own health or that of their families when they are ill, including information for the use of drug and non-drug products. This includes a system for creating health literacy about taking care of one's own health, with and without the use of drugs, using technology such as telemedicine or telepharmacy, or having a health service system that everyone in the community can access with RDU as quality of health care services.