Objective To investigate the effect of berbering on the expression of hypoxiainducible factor1α (HIF-1α) and the neuronal apoptosis after focal cerebral ischemia. Methods Male SD rats were randomly divided into six groups: control (sham surgery), middle cerebral artery occlusion and reperfusion(MCAO/R), MCAO/R treated with vehicle(DMSO), MCAO/R treated with berbering at concentrations of 10mg/kg, 20mg/kg, 40mg/kg,respectively. Berbering of different doses was injected intraperitoneally at 24hours, 48hours before operation and 6hours after operation. We observed the neurological deficits in different groups. Rats were sacrificed at 7days for TTC staining and at 24hours for Nissl staining, immunohistochemical, double fluorescence labeling, TUNEL studies. Results Berbering improved neurological deficits(P<0.05) except at the concentration of 10mg/kg(P>0.05), reduced the infarct volume (P<0.05)dependent of different concentrations. Berbering inhibited the neuronal deformation shown by Nissl staining and reduced the expression of HIF-1α, activated Caspase-3, BNIP3 and VEGF detected by immunohistochemical staining. HIF-1α positive immunoreactive materials were colocalized with BNIP3,Caspase-3 and TUNEL staining inside neurons in the injured cerebral cortex expressed by double fluorescence labeling. Conclusion Berbering may play a neural protection effect by inhi