The resveratrol-induced cardiac protection was studied in Zucker obese rats. Rats were divided into five groups. Groups 1 and 2: lean control (LC) and obese control (OC); group 3: obese rats treated orally with 5 mg/kg/day of resveratrol (OR) for two weeks; group 4: obese rats received 10% glucose solution ad libitum for three weeks (OG); group 5: obese rats received 10% glucose for three weeks and resveratrol (OGR) during the 2^nd and 3^rd weeks. Body weight, serum glucose and insulin were measured, and then hearts were isolated and subjected to 30 min ischemia followed by 120 min reperfusion. Heart rate, coronary flow, aortic flow, developed pressure, the incidence of reperfusion-induced ventricular fibrillation (VF), and infarct size were measured. Resveratrol reduced body weight and serum glucose in the OR compared to the OC values (414±10 g and 7.08±0.41 mmol/l to 378±12 g and 6.11±0.44 mmol/l), but insulin levels were unchanged. Same results were obtained for the OG group vs. OGR group. Resveratrol improved postischemic cardiac function in the presence or absence of glucose intake compared to the resveratrol-free group. The incidence of VF and infarct size were reduced by 83% and 20% in the OR group, 67% and 16% in the OGR group compared to the OC and OG groups, respectively. Resveratrol increased GLUT-4 expression, and reduced endothelin expression and cardiac apoptosis in ischemic/reperfused hearts in the presence or absence of glucose intake. Thus, the protective effect of resveratrol could be related to its direct effects on the heart.