Abstract: Objective To study the relationship between VEGF decreases focal cerebral ischemia/reperfusion injury in rabbits and the expression of cysteinyl aspirate-specific proteinase-3 (caspase-3) protein. Methods Focal cerebral ischemia/reperfusion model in rabbit was induced. The VEGF was administered at 0, 1 and 3 h after reperfusion respectively. Infarct and edema volumes, neurological deficit score, apoptotic cells, and expression of caspase-3 were assessed at 3 d after reperfusion. Results VEGF reduced infarct volumes compared with controls by 23.3% and 17.9% when administered VEGF at 0 and 1 h after reperfusion. Edema volumes, apoptotic cells and expression of caspase-3 in the perifocal regions were significantly lower than that in control group when administered VEGF within 1h after reperfusion (P<0.01). There was no difference when administered VEGF at 3h after reperfusion. Infarct volumes were correlated significantly with expression of caspase-3 in the perifocal regions (P<0.05). Conclusions The effect of VEGF on the expression of caspase-3 is related with the neuroprotective time window. The VEGF can reduce the incidence of neuronal apoptosis during the cerebral ischemia/reperfusion injury by reducing the expression of caspase-3 protein.