(-)-Epigallocatechin gallate (EGCG) exerts multiple beneficial effects on cardiovascular performance. In this study, we aimed to examine the effects of EGCG on diabetic cardiomyopathy during myocardial ischemia/reperfusion (I/R) injury. EGCG (100 mg/kg/day) was administered at week 6 for 2 weeks to diabetic rats following the induction of type 1 diabetes by streptozotocin (STZ). At the end of week 8, the animals were subjected to myocardial I/R injury. The EGCG-elicited structural and functional effects were analyzed. Additionally, EGCG (20 µM) was administered for 24 h to cultured cardiac H9c2 cells under hyperglycemic conditions (30 mM glucose) prior to hypoxia/reoxygenation (H/R) challenge, and its effects on oxidative stress were compared to H9c2 cells transfecteed with silent information regulator 1 (SIRT1) small interfering RNA (siRNA). In rats with STZ-induced diabetes, EGCG treatment ameliorated post-ischemic cardiac dysfunction, decreased the myocardial infarct size, apoptosis and cardiac fibrosis, and reduced the elevated lactate dehydrogenase (LDH) and malonaldehyde (MDA) levels, and attenuated oxidative stress. Furthermore, EGCG significantly reduced H/R injury in cardiac H9c2 cells exposed to high glucose as evidenced by reduced apoptotic cell death and oxidative stress. The protein expression levels of SIRT1 and manganese superoxide dismutase (MnSOD) were reduced in the diabetic rats and the H9c2 cells under hyperglycemic conditions, compared with the control rats following I/R injury and H9c2 cells under normal glucose conditions. EGCG pre-treatment significantly upregulated the levels of htese proteins in vitro and in vivo. However, treatment with EX527 and SIRT1 siRNA blocked the EGCG-mediated cardioprotective effects. Taken together, our data indicate that SIRT1 plays a critical role in the EGCG-mediated amelioration of I/R injury in diabetic rats, which suggests that EGCG may be a promising dietary supplement for the prevention of diabetic cardiomyopathy.