Objective：To explore the protective effect of leptin against rats intestinal ischemia/reperfusion injury and the related mechanism. Methods: Ninety-nine rats were randomly divided into 11 groups (n=9),namely the sham-operation group,ischemia/reperfusion groups (45 min ischemia plus 15 reperfusion \[I45R15\],I45R30,I45R60,I45R180,I45R360)and the 5 corresponding leptin-treated ischemia-reperfusion groups. The serum levels of TNF-α and IL-10 were determined in all groups and the histopathological changes were observed in the small intestine. Results: Compared with the sham-operation group,the serum levels of TNF-α and IL-10 were significantly increased in the ischemia/reperfusion groups (both P<0.05),with obvious pathological damage observed in the ischemia/reperfusion groups. Leptin treatment significantly decreased TNF-α level,increased IL-10 level,and alleviated the damage of the small intestine (all P<0.05) of animals after ischemia /reperfusion injury.Conclusion: Leptin can alleviate the intestinal damage in rats after intestinal ischemia/reperfusion through down-regulating TNF-α level and up-regulating IL-10 levels.