To study the activation of extra-cellular signal regulated kinase (ERK) after focal cerebral ischemia/reperfusion in rats and effect of Naoxintong on it.Methods：Ninety male adult wistar rats were randomly divided into 3 groups，the sham-operated group、the control group and the Naoxintong group．The model of middle cerebral artery occlusion (MCAO) was established by introducing a nylon suture to the right internal carotid artery. Before the ischemic phase, to rats in the sham-operated group and the control group, 4ml of normal saline was intragastric administrated, and to rats in the Naoxintong group, Naoxintong dissolved in 4ml of normal saline(0.48g/kg) was intragastric administrated for 6 days. The rats were decapitated at 3hrs, 6hrs, 24hrs, 48hrs, 72hrs after reperfusion.6 rats of every group at each time point. The volume of infarction were observed by the TTC staining method;The apoptosis neurons were detected in CA1area by TUNEL method ;ERK phosphorylation was detected by immunohistochemistry.Results：The cerebral ischemia induced ERK activation reached the peak at 6hrs and maintained to 72hrs after reperfusion.As compared with the control group,the ERK activation in the Naoxintong group was significantly enhanced with increased positive immune reacted cells(P<0.01). As compared with the control group,the volume of infarction and the apoptosis neurons in the Naoxintong group was significantly decreased(P<0.01). Conclusion：Cerebral ischemia/reperfusion could induce the activation of ERK in the ischemic brain cells,untervention of Naoxintong could enhance the activation and decrease the volume of infarction and the apoptosis neurons ,alleviate the ischemic injury.