Background: Diabetic cardiomyopathy is a specific complication that develops independently of coronary artery disease or hypertension. Previous studies stated the potential role of a state of inflammation via upregulation of NF-kB. The effect of vildagliptin, a DPP-4 inhibitor approved for treatment of T2DM, may be promising in the prevention of diabetic cardiovascular complications. Aim of the work: This study was designed to investigate the efficacy of vildagliptin on FBG and lipid profile and cardiac and blood pressure changes associated with T2DM in fructose induced rat model of insulin resistance to find the exact role of this drug in the recommended ideal protocol of treatment T2DM. Materials and Methods: Animal groups included normal control, non treated fructose induced diabetic and vildagliptin (10 mg/ kg /day p.o. for 4 weeks) treated diabetic groups. We investigated insulin resistance parameters, lipid profile, BP, LV wall thickness, Lead II ECG, histopathological study of the cardiac tissue and GSH and NF-KB concentrations in LV tissue homogenate. Results: Vildagliptin treatment reduced body weight, HOMA-IR, SBP, MABP and R wave height with no change in DBP, LV wall thickness or NF-kB. GSH was significantly elevated. The intercellular gap and extracellular matrix were slightly reduced with less hypertrophied myocardial cells. Conclusion: Vildagliptin failed to reverse insulin resistance or hyperglycemia. It has dual opposite effects on cardiac function. It may exert cardiopretective effect through antioxidant effect. On the contrary, it exerted cardiotoxic effect though the mechanism is unclear.