Abstract: Objective To investigate effect and significance of hydrosamow yellow A (HSYA) on the expression of vascular endothelial growth factor (VEGF) in rats with focal cerebral ischemia reperfusion.Methods With the application of the MCAO (middle cerebral artery occlusion) model, effects of HSYA on the changes in VEGF expression in rats were observed following 2 hours cerebral artery occlusion and ischemia -reperfusion at 1, 3, 6, 9, 12, 24, 72 hours and also at 7 and 14 days by using immunohistochemistry staining. Results VEGF expression in endothelia, neuron and gliocyte in the small vessels around ischemic foci increased at 2-3 h following ischemia. The expression of VEGF in endothelia reached a maximum at 24-72 h following reperfusion, then decreased 7 days later, but was still above normal level at week 2. The expression of neuron and gliocyte reached a maximum at 9-12 h after reperfusion, then decreased at 24-72 h, and no expression could be seen at week 1. HSYA could significantly enhance the expression of VEGF at all time points and decrease in the expression of VEGF could be seen at the late stage of ischemia. Conclusions HSYA could enhance the expression of VEGF following cerebral ischemia, which might be one of mechanisms of its protective effect on the brain system.