Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in individuals with diabetes, for which 65% of deaths are attributable to heart disease or stroke. This study was designed to evaluate the cardioprotective effects of vildagliptin and rosuvastatin alone and in combination on streptozotocin-induced type 2 diabetes (T2DM) in rats. Intraprotenial injection (IP) of nicotinamide (NA) 120 mg/Kg, followed by single IP administration of streptozotocin (STZ) 60 mg/Kg, was used for induction of T2DM in rats. Diabetic rats were divided into 4 groups. Diabetic-ischemic /reperfusion (I-R) non-treated group, Vildagliptin diabetic (I-R) pretreated group, Rosuvastatin diabetic (I-R) pretreated group and Vildagliptin + Rosuvastatin diabetic (I-R) pretreated group. Heart rate, ST segment elevation, Fasting blood glucose (FBG), Serum creatinine phosphokinase (CPK-MB), Troponin-I activity, Lipid profile, Serum Malondyaldehyde (MDA) and Serum Interluken-6 (IL-6) were measured. Both drugs showed significant improvement of electrophysiological and biochemical parameters which was confirmed with histopathological examination.