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Objective To explore the protective effects of erythropoietin (EPO) on myocardium against ischemia-reperfusion injury (IRI). Methods The Langendorff model of isolated rat heart was set up and a 3-stage protocol was performed: 20 min stabilization, 30 min global ischemia, and 120 min reperfusion. Sixty SD rats were randomly divided into sham group, ischemia-reperfusion group (I/R group ) and EPO treated group (EPO group). Heart rate (HR), left ventricular developed pressure (LVDP), the first derivative (△dp/dt max) and coronary flow (CF) were recorded at the 20th minute of stabilization and the 120th minute of reperfusion. Lactate dehydrogenase (LDH) and creatine phosphokinase (CK) in the coronary effluent at the 60th minute of reperfusion, the levels of myocardial nuclear factor-kappa B (NF-KB) and the myocardial content of tumor necrosis factor-α (TNF-α) ,interleukin-1β (IL-1β) were measured at the end of reperfusion. Results No statistically significant differences were observed on the aspect of hemodynamic parameters among the groups at the 20th minute of stabilization, but at the 120th minute of reperfusion, the recovery ratio of EPO group was higher than I/R group (P