Ischemia/Reperfusion (I/R) injury during kidney transplantation is a major clinical problem which leads to delayed graft function or even graft rejection. Therefore, the aim of the present study was to explore the possible protective effects of trimetazidine, an anti-ischemic agent, against experimentally-induced renal I/R injury in rats. Ischemia was induced by bilateral clamping of renal pedicles for 45 min followed by 24 h of reperfusion. Trimetazidine (10 mg/kg) was orally administered twice daily for 14successive days before induction of ischemia. At the end of the reperfusion period (24 h), blood and renal tissue samples were collected for biochemical and histopathological examination. Trimetazidine showed nephroprotective effects as evidenced by significant decrease in blood urea nitrogen and serum creatinine levels as well as renal content of tumor necrosis factor-α, malondialdehyde and myeloperoxidase. In addition, trimetazidine replenished renal content of adenosine triphosphate and glutathione that was confirmed by the improvement in histopathological features. The current study demonstrated the nephroprotective effects of trimetazidine against renal I/R injury, which might be mediated through its anti-ischemic, anti-inflammatory or antioxidant activities.