Aim Middle cerebral artery occlusion/reperfusion (MCAO/R) is a widely used animal model for cerebral ischemiareperfusion injury, which causes great harm to human health.Salvianolic acid A (SalA) from Danshen has been reported to possess various neuroprotection effects in lots of in vitro cell injury models.So in this study,the protection effects of SalA on MCAO/R injury were investigated and the protection mechanism was also discussed.Methods MCAO for 1.5 h followed by 24 h of reperfusion induced severe brain injury.10 mg · kg1 Sa1A was injected intravenously just after 1.5 h MCAO.The neurological deficit scores, infarct volume and cerebral edema were carried out after 24 h of reperfusion.Then the H&E and Nissl staining methods were used to see whether SalA could effectively ameliorated the pathological damages of brain.Then the Western blot assay was performed to study the possible signaling pathway stimulated by SalA.Results SalA (10 mg · kg1) could decrease the neurological deficit scores, infarct volume and cerebral edema of MCAO/R rats significantly (P < 0.01, P < 0.05and P < 0.01).The brain pathological damages of MCAO/R rats could also be effectively ameliorated by the analysis of H&E and Nissl staining results.Western blotting results showed that the upregnlation of Caspase3 in MCAO/R rat brain could be inhibited by SalA (P <0.01).With the administration of SalA, the Bcl2 level in the brain was increased (P <0.01) and the Bax level was decreased (P <0.01) compared with model group.Furthermore,the phosphorylation levels of Akt, GSK3 β and CREB decreased significantly in model group, while SalA treatment could significantly reverse the process (P <0.01, P < 0.05 and P < 0.05).Conclusion These results indicated that SalA administration could protect rat brain against MCAO/R induced injury by ameliorating neurological deftcits, decreasing the infarct volume and cerebral edema.And the antiapoptosis effects of SalA may result from the regulation of PI3K/Akt/GSK3β pathway.