AIM/INTRODUCTION: Analgesic, anti-inflammatory and anti-apoptotic effects of pregabalin have been shown previously. In this study, we investigated the protective effect of different doses of pregabalin on skeletal muscle IR injury in rats. MATERIALS AND METHODS: 24 rats were randomly divided into 4 groups (Control, Ischaemia-Reperfusion (IR), IR-Pregabalin 50 mg, IR-Pregabalin 200 mg). Following IR, serum Ischemia Modified Albumin (IMA) and tissue Paraoxonase (PON) were studied and gastrocnemius muscle tissue was removed for histopathologic examination. RESULTS: Interstitial inflammation was higher in the IR group than in the control and Pregabalin 200 mg groups (p = 0.037, p = 0.037, respectively). Congestion was higher in the IR group than in the control, Pregabalin 50 and 200 mg groups (p = 0.001, p = 0.004, p = 0.004, respectively). PON was lower in the IR group than in the Control, Pregabalin 50 and 200 mg groups (p = 0.001, p = 0.007, p = 0.015, respectively). IMA was higher in the IR group than in the Control, Pregabalin 50 and 200 mg groups (p < 0.0001, all). CONCLUSION: We think that administration of pregabalin, more prominent at 200 mg, can reverse the injury that occurs in the skeletal muscle of IR-induced rats. Pregabalin can be safely used for analgesia in cases of IR.