Objective To investigate the effect of hypoxiainducible factor-1α (HIF-1α) inhibitor(2ME2) on the injury induced by focal cerebral ischemia. Methods Male SD rats were randomly divided into four groups: Control (sham surgery), Middle Cerebral Artery Occlusion and Reperfusion(MCAO), MCAO treated with vehicle(DMSO), MCAO treated with 2ME2. 2ME2 was injected intraperitoneally 1 hour after operation. The neurological deficits were observed in different groups. Rats were sacrificed 7 days later for TTC staining and 24 hours later for Western blotting, Nissl staining, immunohistochemical and TUNEL studies. Results 2ME2 improved neurological deficits(P<0.05), reduced the infarct area (P<0.05), inhibited the neuronal deformation shown by Nissl staining and reduced the expression of HIF-1α, activated Caspase-3, BNIP3 and VEGF detected by Western blotting and immunohistochemical staining.Conclusion 2ME2 is a powerful agent to protect the brain from cerebral ischemic injury by inhibiting HIF-1α activity, attenuating the superfluous expression of VEGF which results in the protection of Blood_Brain_Barrier (BBB) permeability, supp