Abstract： Objective To investigate the mechanism of action of electroacupuncture(EA)at Baihui,Shuigou,Zusanli,and Quchi points in the treatment of cerebral ischemia based on the hypoxia-inducible factor-1α(HIF-1α)-vascular endothelial growth fac-tor(VEGF)-erythropoietin(EPO)signaling pathway.Methods A total of 108 male Sprague-Dawleyrats were randomly divided into sham-operation group,model group,and EA group.The suture method was used to establish a rat model of right middle cerebral artery occlusion(MCAO).At 4 hours after modeling,the rats in the EA group were treated with EA at Baihui,Shui-gou,left Housanli(Zusanli),and Quchi points with dilatational wave at a frequency of 5-100 Hz for 20 minutes each time,once a day for 14 days,and those in the sham-operation group and the model group were caught and fixed without intervention.The modified Neurological Severity Score(mNSS)was used to evaluate neurological deficit;Doppler ultrasound was used to measure the change in regional cerebral blood flow(rCBF)in the ischemic penumbra;HE staining was used to observe the pathological changes of the ischemic penumbra;immunohistochemistry was used to measure the number of CD34-positive cells in the ische-mic penumbra;Western blot and RT-PCR were used to measure the protein and mRNA expression levels of HIF-1α,VEGF,and EPO in the ischemic penumbra.Results Compared with the sham-operation group at each time point,the model group had sig-nificant increases in mNSS score,the number of CD34-positive cells,and the protein and mRNA expression levels of HIF-1α,VEGF,and EPO(P＜0.05)and a significant reduction in rCBF(P＜0.05),with massive neuronal necrosis shown by HE stai-ning.Compared with the model group at each time,the EA group had a significant reduction in mNSS score(P＜0.05)and sig-nificant increases in rCBF,the number of CD34-positive cells,and the protein and mRNA expression levels of HIF-1α,VEGF,and EPO(P＜0.05),with certain improvements in the pathological changes of the ischemic penumbra.Conclusion EA at Baihui,Shuigou,Zusanli,and Quchi points can activate the protein and mRNA expression levels of the HIF-1α-VEGF-EPO pathway,increase the number of CD34-positive cells,and mediate endothelial angiogenesis,thereby improving rCBF and brain structure and function in MCAO rats,and its therapeutic efficacy has a time cumulative effect.