[ABSTRACT] Aim To investigate protection of erythropoietin (EPO) on rat cerebral ischemia-reperfusion injury Methods The model of focal cerebral ischemia-reperfusion injury was made by occluding middle cerebral artery (MCA) . At 2hours or 0hour before or 6hours after cerebral ischemia , EPO intervention group received an intraperitoneal injection of rHu-EPO (3 000 u/kg), while ischemia-reperfusion group ,sham operation group and normal group received same doses of saline. The model was two hours after ischemia-reperfusion.The brains were removed 72hours after reperfusion.Neurological deficit scores apoptosis and expressions of Nissl body neuroglobin and monocyte chemoattractant protein-1 were detected. Results After 72 h reperfusion, Nissl body of ischemia-reperfusion group was significantly less than EPO-intervention group, sham-operated group, normal group. ischemia-reperfusion group neuroglobin and monocyte chemoattractant protein-1 expression was significantly higher than sham operation group and normal group (P <0. 01), with ischemia-reperfusion group compared with ，EPO-intervention group neuroglobin expression increased significantly (P <0. 05), monocyte chemoattractant protein-1 expression was significantly lower (P <0. 01). Conclusions EPO may be raised neuroglobin and lowered monocyte chemoattractant protein-1 expression, which can provide protective effect on cerebral ischemic-repefusion injury in rats.