Aim To investigate the protective effect of capsaicin on renal ischemia reperfusion injury in rats and its mechanism. Methods 50 male SD rats were divided into sham operation group (Sham), renal ischemia-reperfusion injury group (IRI) and low, middle and high dose capsaicin group. The model of renal ischemia reperfusion injury was established by clamping bilateral renal pedicle for ischemia 45 min, and reperfusion 24 h. Then rats were killed by excessive anesthesia and kidney and serum were collected. Serum creatinine (SCr), urea nitrogen (BUN), cell apoptosis and pathologic renal tissue were detected, mitochondrial adenosine triphosphate (ATP), malondialdehyde (MDA) content, Ca²⁺-ATP enzyme,Na⁺-K⁺-ATP enzyme, catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity were measured. Results Capsaicin intervention can reduce BUN, SCr, cell apoptosis and the pathological change of kidney tissue, increase Ca²⁺-ATP, Na⁺-K⁺-ATP, CAT, GPx and SOD enzyme activity and ATP content and decrease the level of MDA in mitochondria. Conclusion Capsaicin has protective effects on renal ischemia-reperfusion injury in a concentration dependent-manner and its mechanism is related to the inhibition of lipid peroxidation.