ARDS (Acute respiratory distress syndrome) is due to injury of alveolar cells the reasons of which may be multiple including septic infections and toxic chemicals. Such injury leads to edema due to leakage of alveolar epithelial cells. Since claudins regulate paracellular permeability of cell layers evidently changes in claudin expression are involved in such disease. There are no morphological studies on claudin expression by human tissues in ARDS. Evidence of tight junctional protein changes in ARDS can be obtained from animal experiments or cell culture studies. In alveolar cells cultured from septic rat lung a decrease of claudin 4, claudin 18 and occludin was found associated with a decrease in transmembrane resistance [68] . In ventilator-induced lung injury in mice the mRNA expression of claudin 4 increased after 3 hours [69] . Such a phenomenon appears to be an adaptive mechanism to make the alveolar layers tighter, since blocking specifically the mRNA synthesis of claudin 4 by siRNA or CPE lowers the transmembrane potential [69] . Similar results come from experimentally induced pancreatitis in rats where the mRNA levels of claudin 4, claudin 5 and occludin decreased due to pancreatitis induced lung injury but increased after administration of emodin, a chemical suggested to enhance epithelial barrier function [70] . Such data emphasize especially the role of claudin 4 in combating the abrogation of alveolar cell permeability in lung injury. Also the expression of claudin 5 is important for endothelial cell tightness and vascular permeability. Acrolein present in tobacco smoke may cause lung injury by influencing claudin 5 expression in endothelial cells and mice more resistant to acrolein have a better survival due to their increased expression of claudin 5 mRNA transcripts [71] .