Objective:It is proved that the pretreatment of oleanolic acid(OA) increases rat’s hepatic glycogen and alleviates the hepatic ischemic reperfusion injury(HIRI),but the mechanism is still not quite clear. This research is focused on the influence of OA pretreatment to rat’s PI3K-AKT-GSK-3β signaling pathway around its HIRI. Methods:Total of 128 male Sprague-Dawley(SD) rats were indvided into sham group(SH),ischemic reperfusion group(IR),0.5% sodium carboxymethycellulose(CMC-Na) group(CM),OA+0.5% CMC-Na group(OA) equally. Before operation all rats got intragastric administration one time a day for seven days,OA group with OA(100 mg/kg)+0.5% CMC-Na,SH group and IR group with water of the same volume,CM group with 0.5% CMC-Na of the same volume. At the 8th day,rats were suffered from segmental(70%) hepatic ischemia for 60 min and were followed by different periods of reperfusion. In the 8th day before the operation,the hepatic tissu were reperfused at the point of 0 h,3 h,and 6 h. The protein expressions of p-PI3K(p85),p-AKT(ser473),AKT,p-GSK-3β(ser9) and GSK-3β were evaluated. Results:Before operation,at the point of 0h,the protein expressions of p-PI3K(p85),p-AKT(ser473)and p-GSK-3β(ser9) in the OA group increased much more remarkably than other three groups(P < 0.05),while the protein expresions of SH group,IR group and CM group were no differences(P > 0.05). At the reperfusion point of 3 h,6 h,the protein expressions of p-PI3K(p85),p-AKT(ser473)and p-GSK-3β(ser9) in the OA group increased much more remarkably than other three groups(P < 0.05),while the protein expressions of SH group were lower than those of other three groups(P < 0.05). There was no difference between IR and CM group in the 3 proteins expression(P > 0.05). The protein expressions of AKT and GSK-3β in all the groups at all the points were no differences(P > 0.05). Conclusion:The pretreated OA increases the protein expressions of p-PI3K(p85),p-AKT(ser473)and p-GSK-3β(ser9) before and after HIRI,activating the signaling pathway of hepatic PI3K-AKT-GSK-3β,which may be one of the mechanisms of OA alleviating HIRI.