To observe the effect of hydroxy safflower yellow A(HSYA)combined with paeoniflorin on expressions of PI3K and Akt mRNA in PI3K/Akt signal pathway of rats with acute focal cerebral ischemia reperfusion injuries.Methods：Divided 60 SPF male SD rats into 6 groups，namely the model group，sham operation group，HSYA group，paeoniflorin group，Ginkgolide group，and the combination group，10 rats in each group.Replicated the model of cerebral ischemia reperfusion.After one hour of cerebral ischemia and 6 hours of perfusion the rats were medicated related intravenous injection from posterior caudal vein for 7 days，once a day，continuously HSYA group was given 5.0 mg/(kg·d)of HSYA solution by gavage.Paeoniflorin group was given 5.0 mg/(kg·d)of paeoniflorin solution by gavage.The combination group received5.0 mg/(kg·d)of HSYA combined with 5.0 mg/(kg·d)of paeoniflorin by gavage.Ginkgolide group was given5.0 mg/(kg·d)of Ginkgolide injection by gavage.The model group and sham operation group were given the same amount of normal saline.Collected corresponding samples after 2 hours of the last time of administration，and then reserved them.Detected expressions of PI3K and Akt mRNA in hippocampus of rats by qRT-PCR(quantitative real-time polymerase chain reaction)method.Results：PI3K mRNA expression levels in rats in the model group were obviously reduced in comparison with those in the sham operation group，the difference being significant(P＜0.01).PI3KmRNA expression levels in hippocampus of rats in HSYA group， paeoniflorin group， Ginkgolide group， and the combination group were evidently declined by comparing with those in the model group，differences being significant(P＜0.05).PI3K mRNA expression levels of rats were higher in HSYA group and Ginkgolide group in comparison with those of the combination group，differences being significant(P＜0.05).Conclusion：The protection mechanism of the combined medications of HSYA and paeoniflorin for rat model of cerebral ischemia reperfusion injuries may be relevant to the evident adjustment of PI3K mRNA over-expression in PI3K/Akt signal pathway and the micro adjustment of Akt mRNA over-expression.