Heart failure is a functional or structural heart disorder impairing ventricular filling or ejection of blood to the systemic circulation. T2DM is a metabolic disease characterized by chronic hyperglycemia, considered an important cause of heart failure. Dapagliflozin, a member of the SGLT2 inhibitor class, improve glycemic control in adults with T2DM and reduce the risk of hospitalization for heart failure. The American College of Cardiology (ACC) recently released calls for use of dapagliflozin in HFrEf with or without diabetes mellitus. Aim of the study: The present study was designed to evaluate the effect of dapagliflozin in-vivo in the experimentally induced HF with and without T2DM on body weight, FBG, ECG, NT-pro BNP, LVW/WHW and histopathological changes. And also, in-vitro on isolated mammalian heart and isolated strips of rabbit aorta. Materials and methods: Rats for in-vivo study, were classified into: Group I: control normal group. Group II: non treated diabetic group of HF(diseased group). Group III: It was treated with dapagliflozin for 4 weeks. Group IV:non treated non diabetic group of HF(diseased group). Group V: It was treated with dapagliflozin for 4 weeks. Rabbits for in-vitro experiments on isolated heart and strips of aorta. Results: Regarding in-vivo study, treated groups showed significant improvement in all parameters and improvement of the histopathological changes. Regarding in-vitro study, dapagliflozin produced neither effect on isolated mammalian heart nor on isolated strips of rabbit aorta. Conclusion: Dapagliflozin showed improvement of parameters of HF with or without diabetes mellitus. Dapagliflozin has protective cardiac effects.