Abstract: Objective: To investige the effect of EPO on hypoxia cardiomyocytes and evaluate the possible molecular protective mechanism. Methods: The survival,apoptotic and necrotic rates of cardiomyocytes were assessed by flow cytometry. Cardiomyocytes were divided into three groups: normal group,hypoxia group and hypoxia treated with EPO group.Bcl-2,Bax,Caspase-3 mRNA levels were determined by Northern-blot analysis while cytochrome C,STAT-3,Caspase-3 protein levels were determined by Western-blot analysis in each group. Results: The survival,apoptotic and necrotic rates of three groups were significantly different（92.1% vs 70.9% vs 89.0%,2.3% vs 18.73% vs 6.0%,3.5% vs 8.0% vs 3.5%,P＜0.01）.At the concentration of 1U/mL of EPO,the protective effects occured,the effects of 5U/mL,25U/mL,and 125U/mL of EPO were similar. Compared with the hypoxia group,the expressions of Bcl-2 mRNA and STAT-3 protein were upregulated while the expressions of Bax,Caspase-3 mRNA and Caspase-3 protein were downregulated significantly in EPO group（P＜0.01）. Conclusion: The optimized concentration for EPO to make effect was 5U/mL.Hypoxia cardiomyocytes were protected by activating JAK-STAT signaling pathway in EPO group.