Objective To investigate the effect of hypoxiainducible factor-1α gene on the proliferation and differentiation of neural stem cells after focal cerebral ischemia in rats, and to explore the mechanism of the effect. Methods Middle cerebral artery occlusion(MCAO) and reperfusion models were established and divided into sham group, NS group, AD group and AdHIF-lα group. NS, AD and Ad-HIF-lα were injected into the ischemic ventricle respectively. The mNSS was evaluated the expression of EPO was observed, and the number of BrdU positive cells in subventricular zone and that of BrdU／NF200， BrdU／GFAP double labeled cells in cortex were calculated by immumofluorescence method. Results The mNSS were statistically different between Ad-HIF-lα group and the other three groups; the expression of EPO was higher in Ad-HIF-lα group; the number of BrdU positive cells increased obviously in Ad-HIF-lα group; the cellular rebirth and differentiation demonstrated that there existed a significant difference (P<0.05) in the numbers of BrdU／NF200