Diabetic cardiovascular complications are a leading cause for increased morbidity and mortality. Diabetic cardiomyopathy is one of these complications which develop independently of coronary artery disease or hypertension. Previous studies stated the potential role of a state of inflammation via upregulation of NF-kB. The extra pancreatic, diuretic effect of canagliflozin, a SGLT2 inhibitor, appears promising in treatment of diabetic cardiomyopathy or reversing cardiovascular side effects of insulin sensitizers. This study was designed to investigate the potential cardio-protective effects of canagliflozin alone and in combination with metformin on fructose induced rat model of insulin resistance. Forty male albino rats were divided into 5 groups: normal control group, non-treated fructose induced diabetic group, canagliflozin treated group (28 mg/kg/day), metformin treated group (250 mg/ kg /day) and canagliflozin+ metformin treated group. All drugs were given p.o. for 4 weeks. 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 were investigated. Canagliflozin+ metformin combination showed more significant improvement of electrophysiological and biochemical parameters which were confirmed with histopathological examination than other groups, suggesting a very promising role of this combination in treatment of insulin resistance.