Saxagliptin (Dpp-4 inhibitor) is a newer anti-diabetic drug for type 2 diabetes mellitus. It has beneficial effect on glycemic control and weight neutral but its effects on the heart during ischemic reperfusion periods are not known. We investigated the effect of Saxagliptin on infarct size in a clinically relevant cardiac I/R injury model in type 2 diabetic rats and its underlying cardioprotective effects. Normal and diabetic rats were randomized to receive Saxagliptin 5 mg/kg b.wt. orally for a period of 4 weeks and were subjected to 30 min left anterior descending artery coronary artery occlusion followed by 4 h of reperfusion. Percentage left ventricle infarction, cardiac biomarkers (SGOT, CK, CKMB) oxidative stress markers (malondialdehyde, catalase, SOD) were analysed. When compared to control group, saxagliptin produced significant dose-dependent reduction in percentage infarct volume. Saxagliptin, at 5 mg/kg b.wt. dose, there was a significant reduction in SGOT, CK CKMB and MDA levels and in contrast there was a significant increase in anti-oxidant enzymes such as SOD and catalase levels. Saxagliptin decreases infarct size and showed significant cardioprotective action mediated by antioxidant mechanisms.