BACKGROUND Tramadol has been shown to decrease ischemia-reperfusion injuries in myocardial or brain tissues. The aim of this study was to assess the effects of tramadol on ischemia-reperfusion injury in a rat hind limb ischemia-reperfusion model. METHODS Forty-five healthy adult male Wistar rats were randomized into three experimental groups as follows: Sham, Ischemia-reperfusion and Ischemia-reperfusion + tramadol groups. Ischemia was induced in anesthetized rats by left femoral artery clipping for 2 h followed by 24 h of reperfusion. Tramadol (20 mg/kg) was administered intravenously immediately prior to reperfusion. Blood pH, pO2, pCO2, HCO3, creatine phosphokinase (CPK), lactate dehydrogenase (LDH) as well as plasma malondialdehyde (MDA) were measured at the end of the reperfusion. Left gastrocnemius muscle samples were taken for histological and biochemical examination. RESULTS The pH and pCO2 were similar in all study groups, with no statistical significance. pO2 and HCO3 levels presented the highest elevation in sham and Ischemia-reperfusion + tramadol groups, as compared to Ischemia-reperfusion group (P < 0.05). The extent of muscle changes in the ischemia-reperfusion + tramadol group was significantly lower than ischemia-reperfusion group (P < 0.05). In comparison with other groups, serum and tissue MDA levels in ischemia-reperfusion group were significantly increased (P < 0.05). The muscle tissue glutathione (GSH), superoxide dismutases (SOD) and catalase (CAT) levels in the Ischemia-reperfusion group were significantly lower than the other groups (P < 0.05). Wet/dried weight ratio in ischemia-reperfusion group was significantly higher (P < 0.05) than subjects in other groups. CONCLUSIONS From the histological, histochemical and serum biochemical perspective, the treatment with tramadol has alleviated the metabolic injuries in the skeletal muscle ischemia and reperfusion in this experimental model.