Objective To explore the mechanism of Houshi Hei San (Hou's Black Powder) against cerebral ischemia damage by observing effects of wind-dispelling drugs (WDD), deficiency-tonifying drugs (DTD) and combined WDD-DTD in Houshi Hei San on the expressions of Brain-derived neurotrophic factor (BDNF), Phosphatidylinositol 3-kinase (PI3K), Protein Kinase B (PKB, also called Akt), and cyclic adenosine monophosphate response element binding protein (CREB).Methods Rats were subjected to permanent middle cerebral artery occlusion ( pMCAO ) surgery and randomly divided into the sham-operation group, model group, WDD group, DTD group and combined WDD-DTD group.At 72 hours after cerebral ischemia, protein of ischemic hippocampus was extracted from the fresh brain.The expression of BDNF was detected by using ABC-ELISA;PI3K, Akt and CREB were analyzed by using western blot.Results WDD had little effect on neurological deficits score and no remarkable effect on the expression levels of BDNF, PI3K, Akt and CREB;DTD up-regulated the expression of BDNF and Akt markedly (P <0.05);combined WDD-DTD significantly up-regulated the expression level of BDNF, PI3K, and Akt as well as CREB in the ischemic hippocampus, as compared to the model group (P<0.05).Conclusion WDD could assist DTD in Houshi Hei San against cerebral ischemic damage by regulating the key molecular signal of PI3K/Akt.