Abstract Background: Although the tourniquet has been using for hemostasis for the long time, liver dysfunctions following ischemia-reperfusion injuries are common. Tramadol hydrochloride is an opioid drug that decreases the inflammatory response. In this study, the effect of this drug on the liver following ischemia-reperfusion injuries of hind limb in the rat was evaluated. Materials and methods: A total of 30 male Wistar rats were divided into two groups with fifteen rats in each group. Ischemia-reperfusion condition has been formed through blocking the femoral artery for two hours occlusion and 24 hours reperfusion. An ischemia-reperfusion group (I/R) did not receive the drug, while the treatment group received the drug (20mg/kg) intravenously, immediately after reperfusion. Results: In I/R group the level of both alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly increased compered to treatment group (P<0.05). Also, histopathological damage in liver tissue was significantly increased in I/R group compered to treatment group (P<0.05). Conclusion: Tramadol hydrochloride has liver protective effects against ischemia-reperfusion injuries which could use it to alleviate the ischemia-reperfusion injuries causing by tourniquet.