Objective:To study the mechanisms of erythropoietin in protecting cardiac function in diabetic rats. Methods:Forty male SD rats were randomly divided into the control group,the control-EPO group,the diabetic group and the diabetic-EPO group (n=10 for each). The diabetic model was induced by streptozotoein (STZ). In the control-EPO and the diabetic-EPO group,rats were treated with 1 000 IU/kg EPO by subcutaneous injection once per week for twelve weeks. At the seventh day after the last administration,echocardiography was conducted. Blood samples from tail vein were collected for blood glucose and red blood cell numbers measurements. After rats were sacrificed,myocardial tissues were collected,quantitative real-time PCR (RT-PCR) was used to detect the mRNA level of GRP78,SERCA2a and EPOR, and Western blot was used to detect the protein expression of GRP78,SERCA2a and EPOR. Results:Compared with the control and control-EPO group,in the diabetic group,ejection fraction (EF) and LV fractional shortening (LVFS) were decreased significantly (P﹤0.01),blood glucose was increased significantly (P﹤0.01),the mRNA level and the protein expression of GRP78 were increased significantly (P﹤0.01),the mRNA level and the protein expression of SERCA2a and EPOR were decreased significantly (P﹤0.01). EF and LVFS were increased significantly in EPO-treated diabetic rats (P﹤0.01). Diabetic rats receiving EPO administration showed a significantly decrease in the mRNA level and the protein expression of GRP78 compared with the diabetic group (P﹤0.01). EPO treatment significantly increased the mRNA level and the protein expression level of SERCA2a and EPOR (P﹤0.01). Conclusion:EPO treatment can improve the cardiac function,which might be related to the inhibition of endoplasmic reticulum stress,up-regulating of the SERCA2a and EPOR expression.