Objective To investigate the effects of erythropoietin (EPO) on myocardial apoptosis and protein kinase B (AKT) expression in rats of chronic heart failure (CHF). Methods Thirty male adult SD rats were randomly divided into two groups, sham-operated (Sham) group (n = 6) and model (Model) group (n = 24). The abdominal aortic coarctation was used to build CHF model. Sixteen survived rats after operation were randomly divided into two groups including EPO group and control (Control) group. EPO group was received 3 000 U/kg EPO intraperitoneal injection 3 times / week for 4 weeks, and Sham group and Control group were received same volume of normal saline. The echocardiography was used to evaluate cardiac function after 4 weeks, 8 weeks and 12 weeks of treatment. After 12 weeks, all rats were sacrificed after 24 h fasting. The cell morphology and myocardial apoptosis were observed, and apoptosis index (AI) was calculated. Myocardial P-AKT / AKT protein expression was detected by Western blot assay. Results Echocardiography showed that ventricular hypertrophy was found in model group after four weeks, heart failure 8 weeks. Compared with Control group, left ventricular ejection fraction (LVEF) was significantly higher after EPO intervention for 4 weeks (P < 0.05), systolic interventricular septum thickness (IVSs), end-systolic left ventricular posterior wall thickness (LVPWs), diastolic interventricular septum thickness (IVSd), after left ventricular end-diastolic wall thickness (LVPWd) were significantly lower (P < 0.05). The value of AI was significantly lower in EPO group than that of Control group (23.87%±1.45% vs 35.58%±2.81%, P < 0.01). The OD value of P-AKT / AKT was significantly decreased in Control group (0.35±0.06) than that of Sham group (0.81±0.17), the value was significantly increased in EPO group (1.61±0.16) than that of Control group (P < 0.01). Conclusion EPO can improve heart function, inhibit myocardial apoptosis, and promote pro-phosphorylation of AKT in rats with chronic heart failure. [ABSTRACT FROM AUTHOR]