OBJECTIVE: This study examined the changes of neural stem cells (NSCs) following hypoxic-ischemic brain damage (HIBD) in order to provide a basis for clinical use of NSCs. METHODS: Neonatal 7-day-old rats were randomly assigned into three groups: Normal control, Hypoxic and Hypoxic-ischemic groups. The Hypoxic-ischemic group was subjected to the left common carotid artery ligation followed by 8% oxygen exposure for 2.5 hrs.The Hypoxic group was exposed to 8% oxygen for 2.5 hrs but without the carotid artery ligation.The subjects were sacrificed at 3 and 6 hrs, and 1, 3, 7, 14 and 21days after hypoxia/ischemia (10 rats at each time point). The number of NSCs from brain tissues of rats was detected with hematoxylin-eosin staining and immunohistochemistry. RESULTS: NSCs were presented in the normal brain tissues of neonatal rats and were reduced at 10 days postnatal.The NSCs in the Hypoxic and the Hypoxic-ischemic groups increased after hypoxia/ischemia and were significantly higher than that in the Normal control group at 6 hrs after hypoxia and at 1 day after hypoxia-ischemia. The NSCs number peaked at 3 days after hypoxia/ischemia and then decreased gradually but remained higher than that in the Normal control group at 21 days after hypoxia. CONCLUSIONS: NSCs may proliferate in the early phase of HIBD but decrease while the damage is developing. Early NSCs intervention for the treatment of HIBD appears to be promising.