Diabetic rats are more susceptible to myocardial ischemia-reperfusion injury than control rats. The aim of the present study was to evaluate the cardioprotective effect of gallic acid (GA) on isolated rat hearts with alloxan-induced diabetes mellitus. Adult male Sprague-Dawley rats were divided randomly into three groups: control, untreated diabetic and diabetic animals treated with (GA, 25mg/kg). Diabetes was induced by 120mg/kg alloxan injection. Eight weeks after GA administration, the hearts were isolated and exposed to myocardial ischemia-reperfusion. The body weight, blood glucose, hypertrophy index, left ventricular function, infarct size, cardiac markers and oxidative stress were measured. In the diabetic group, body weight, cardiac contractility (±dp/dt), glutathione peroxidase (GPx) level (p<0.001), left ventricular developed pressure (LVDP), rate pressure product (RPP), superoxide dismutase (SOD) and catalase (CAT) levels (p<0.01) as well as the heart weight (p<0.05) significantly reduced. However, blood glucose, infarct size, hypertrophy index, lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB, p<0.001) and troponin-I (cTnI) levels (p<0.05) significantly increased in the diabetic rats compared with the control group. Nevertheless, administration of GA improved significantly LVDP, ±dp/dt, infarct size, LDH, CK-MB (p<0.001), blood glucose, the heart weight (p<0.01), body weight, RPP, hypertrophy index, antioxidant enzyme and cTnI levels (p<0.05) in the diabetic rats. The results of this study indicated that in the diabetic rats, left ventricular dysfunction and hypertrophy significantly induced possibly by oxidative stress. Moreover, GA as a potent antioxidant improved both left ventricular dysfunction and hypertrophy.