Epo hormone has recently shown protective effects against ischemic damage in different organs such as cerebral and renal ischemia. In this study we demonstrated the protective effect of EPO against the experimentally induced heart failure by Adriamycin treatment and against the experimentally induced myocardial infarction. We evaluated the role of Epo by measuring the improvement of cardiac functions in the rats treated with EPO compared to others. Both in vivo by short axis echocardiography and in vitro by isolated heart perfusion study. The possible mechanisms were also evaluated by immunohistochemical staining and revealed the inhibition of Caspase-3 activity and the increase in the angiogenic marker CD31 in EPO treated animals compared to others.