Abstract： Objective： To observe the protective effect of acupuncture preconditioning on blood- brain barrier(BBB) of neonatal rats with hypoxic ischemic encephalopathy(HIE)，and to explore the mechanism of acupuncture for HIE. Methods：A total of 70 SPF neonatal rats were randomly divided into the sham operation group，the model group and the acupuncture preconditioning group. Except for the sham operation group，HIE models were established by ligating the left common carotid artery and keeping hypoxia for 3.5 hours. Sports ability of experimental animals was evaluated by hanging test；pathological changes in nerve cells after hypoxia- ischemia were observed by hematoxylin- eosin(HE) staining；BBB ultrastructure was observed by transmission electron microscope；water contents were measured by dry-wet method；protein expressions of Occludin and tight junction protein zona occludens-1(ZO-1) after cerebral hypoxia ischemia were detected by Western blot. Results：Compared with those in the sham operation group，the duration of hanging test in the model group was shortened (P＜0.05)；water content in hypoxic ischemic brain tissue was increased(P＜0.05)；the protein expressions of Occludin and ZO-1 in cortex tissue were decreased(P＜0.05). Compared with those in the model group，the duration of hanging test in the acupuncture preconditioning group was increased(P＜0.05)；water content in hypoxic ischemic brain tissue was decreased (P＜0.05)；the protein expressions of Occludin and ZO-1 in cortex tissue were increased(P＜0.05). Conclusion：Acupuncture can maintain BBB integrity by up- regulating protein expressions of Occludin and ZO-1，so as to improve hypoxic ischemic brain injury.