Aim To investigate protection of erythropoietin(EPO)on rat cerebral ischemia.Methods The model of focal cerebral ischemia-reperfusion injury was made by occluding middle cerebral artery(MCA).At 2 hours before cerebral ischemia,EPO group received an intraperitoneal injection of rHu-EPO(3 000 u/kg),while ischemia-reperfusion group and sham operation group received same doses of saline.The brains were removed 24 hours after reperfusion.Apoptosis and expressions of heat shock protein 27(HSP27)and vascular endothelial growth factor(VEGF)were detected.Results After 24 hours of reperfusion,it was thus clear that ischemia-reperfusion group(67.48±11.17 cells/HP)had major POD masculine cells,EPO group(45.25±4.72 cells/HP)was decreased,there was significant difference between the two groups(p<0.01),no TUNEL positive cell was found in control group and sham operation group.Compared with ischemia-reperfusion group(25.60±4.42 cells/HP),the expression of HSP27 in EPO group was increased(67.56±13.84 cells/HP,p<0.01).About the expression of VEGF,there was significant difference between EPO group and ischemia-reperfusion group(74.90±11.64 cells/HP vs 40.14±7.50 cells/HP,p<0.01).Conclusion EPO pretreatment could inhibit apoptosis of cortical neurons after cerebral ischemia-reperfusion injury,partially mediated by the up-regulation of HSP27 and VEGF expression.