Abstract: OBJECTIVE To investigate the inhibitive effect of Gualou Guizhi granule(GLGZG) on nerve cell apoptosis in cerebral ischemia-reperfusion injury rat through activatig PI3K/nAKT pathway. METHODS Thirty-six male SD rats were divided into sham operation group, middle cerebral artery occlusion(MCAO) model group and GLGZG group, 12 for each group. MCAO model group and GLGZG group subjected to focal cerebral ischemia reperfusion with suture-occluded induced MCAO method. GLGZG was gave by intragastric administration, once daily for 7 d. Neurobehavioral deficit was performed with modified neurological severity score(mNSS) scale. MRI was used to observe the cerebral infarct volume in rats. PI3K, Akt mRNA were detected by qRT-PCR in the infarcted cortex. The protein expression of PI3K(p85), p-Akt, PDK1, Bcl-2, Bcl-xL, cleaved-caspase-3, Bad, Bax were detected by Western blot. RESULTS The mNSS score of GLGZG group was reduced compared with the MACO model group, especially on 5th and 7th day(P<0.05). Compared with MCAO group, the cerebral infarct volume in GLGZG group rats were decreased significantly(P<0.05) and upregulated the proteins expression of PI3K(p85), p-Akt, PDK1, Bcl-2, Bcl-xL(P<0.01), downregulated cleaved-caspase-3, Bad, Bax(P<0.01), however, the protein expression of Akt was not change. CONCLUSION GLGZG can improve the nerve function deficit of MCAO rat and inhibit the apoptosis of neural cell, which may be associated with activating the PI3K/AKT pathway.