OBJECTIVE: To study the effect of grape seed procyanidins on protein expressions of cysteine aspartic protease 3 (Caspase-3), tumor necrosis factor-related receptors (TRAF6) in renal tissue of rats with renal ischemia-reperfusion injury (RIRI), and explore the protective mechanism of procyanidins on RIRI. METHODS: 50 rats were randomly divided into sham operation group, model group, Shenfukang capsules group (positive control, 600 mg/kg), procyanidins low-dose, high-dose groups (100, 150 mg/kg), 10 in each group. All rats were intragastrically administrated once a day, for 7 d. After administration,rats in other groups except for sham operation group were established the RIRI model.After the modeling successed of 24 h,levels of creatinine (Cr), urea nitrogen (BUN) in serum, and protein expressions of Caspase-3, TRAF6 in renal tissue of rats in each group were detected, and apoptotic rate of renal tubular epithelial cells was determined. RESULTS: Compared with sham operation group, levels of Cr, BUN in serum in model group were significantly increased (P<0.05); protein expressions of Caspase-3, TRAF6 in renal tissue were obviously enhanced (P<0.05); apoptotic rate of renal tubular epithelial cells was obviously increased (P<0.05). Compared with model group, levels of Cr, BUN in serum in each administration group were obviously decreased (P<0.05); protein expressions of Caspase-3, TRAF6 in renal tissue were obviously weakened (P<0.05); apoptotic rate of renal tubular epithelial cells was obviously decreased (P<0.05); and procyanidins high-dose group showed superior effect to low-dose group and Shenfukang granules group (P<0.05). CONCLUSIONS: Grape seed procyanidins can relieve the RIRI of rats, which may be achieved by reducing protein expressions of Caspase-3 and TRAF6 to inhibit the apoptotic rate of renal tubular epithelial cells.