Objective: Various studies show that smoking can influence serum levels of tumor markers such as carcino embryonic antigen (CEA) and kinase or phosphatase enzymes. The main aim of this study was to determine the pathological effects of waterpipe smoking on serum levels of CEA, alkaline phosphatase (ALP) or creatine kinase (CK) in male and female rats. Method: Male and female Wistar rats were randomly divided into control and waterpipe smoking groups of 5 in each. After a period of 10 weeks, blood samples were collected using cardiac puncture method. Following serum collection, serum CEA, alkaline phosphatase or creatine kinase levels were measured. Intestinal tissue was also examined histologically. Data were statistically analyzed and compared between groups using ANOVA.