Diabetes can be considered as a state of chronic inflammation and oxidative stress. Excessive oxidative stress is implicated in the pathogenesis of all diabetic complications. Heme oxygenase-1 is an antioxidant enzyme that is upregulated in response to a variety of insults as a protective mechanism. Resveratrol (RSV) is a polyphenol that exhibits promising pharmacological effects in a variety of disease models. In this study, we investigated the role of RSV in prevention of early pathological changes in the diabetic heart as well as the role of hemeoxygenase-1 in this regard. To achieve this aim, diabetes was induced by ip injection of streptozotocin (50 mg/kg). The rats were divided into 5 experimental groups; normal control (CTR), diabetic control (DM), diabetic rats treated with RSV (DM+RSV); 10 mg/kg) in drinking water, diabetic rats treated with a combination of RSV and an HO-1 inhibitor, Zinc protoporphyrin (ZnPP), (DM + RSV+ZnPP); 10 µmole/Kg/week I.P) and diabetic rats treated with ZnPP alone (DM + ZnPP). Induction of diabetes was accompanied by a significant increase in cardiac MDA level and TGF-β protein expression as well as a significant reduction in eNOS and HO-1 expression. Chronic treatment with RSV significantly attenuated the abovementioned biochemical changes associated with diabetes in addition to alleviation of diabetes-induced histopathological alterations. Furthermore, the effect of RSV was diminished when the HO-1 activity was blocked by ZnPP. These results demonstrate the role of HO-1 in mediating RSV protective effects against diabetes-induced early cardiomyopathy.