Abstract: AIM:To observe whether resveratrol (RSV) attenuates myocardial ischemia/reperfusion injury (MI/RI) in type II diabetes mellitus (T2DM) and, if so, to further investigate the underlying mechanisms. METHODS: T2DM was induced by a high-fat diet (HD) plus low-dose i.p. streptozotocin (STZ) injection. Mice were treated with 10 mg/kg RSV daily by intragastric administration for 3 weeks after acknowledgement of T2DM. Mice were divided into six groups: sham group, I/R group, T2DM sham group, T2DM+I/R group, RSV group, and CpC group. After 30 min ischemia by slip-knot ligature of the left anterior descending coronary artery, myocardium was reperfused for 3 h after knot release (for apoptosis by TUNEL, caspase-3 activity by ELISA) or 24 h (for infarct size determination by TTC staining). At 1 h before MI/RI, compound C (an AMPK inhibitor) was administered i.p. (20 mg/kg). RESULTS: HD feeding plus low-dose STZ injection successfully induced T2DM. RSV alleviated MI/RI in diabetic mice as evidenced by decreased infarct size, cardiomyocyte apoptosis (P<0.01) and caspase-3 activity (P<0.05). RSV treatment also improved APN level both in plasma and adipose tissue in diabetic mice (all P<0.01). Conversely, administration of AMPK inhibitor compound C significantly attenuated the cardioprotective effects of RSV (all P<0.05). CONCLUSION: RSV upregulates adiponectin levels in both plasma and adipose tissue in T2DM, thus attenuating MI/RI.