Objective To evaluate the role of Wnt/β-catenin signaling pathway in lithium chloride preconditioning-induced improvement in postoperative cognitive function of aged rats.Methods A total of 100 pathogen-free healthy male Sprague-Dawley rats,aged 18 months,weighing 540-650 g,were divided into 5 groups (n =20 each) using a random number table:control group (group C),surgery group (group S),lithium chloride preconditioning group (group L),secreted frizzled-related protein 1 (sFRP-1) group (group F) and lithium chloride preconditioning plus sFRP-1 group (group L+F).Lithium chloride 2 mmol/kg was intraperitoneally injected once a day for 5 consecutive days before operation in L and L+ F groups.In F and L + F groups,sFRP-1 10 μl (concentration 10 μg/ml) was injected into the ventricle at 1 day before operation.Ten rats in each group were randomly sacrificed at 1 day after operation,and the hippocampi were removed for determination of the expression of phosphorylated glycogen synthase kinase-3 beta (p-GSK-3β),3-catenin and Wnt in hippocampal tissues (by Western blot).The rest rats underwent Morris water maze test at day 3-7 after operation,and the concentrations of amyloid beta 42 (A3-42) and phosphorylated tau-181 protein (p-tau-181) in cerebrospinal fluid (CSF) were detected by enzyme-linked immunosorbent assay at day 7 after operation.Results Compared with group C,the escape latency was significantly prolonged at 3-7 days after operation,and the concentration of Aβ-42 in CSF was increased in the other four groups,and the expression of Wnt,p-GSK-3β and β-catenin in hippocampal tissues was down-regulated in group S,the expression of Wnt,p-GSK-3β and β-catenin in hippocampal tissues was significantly up-regulated in L and L+F groups,and the concentration of p-tau-181 in CSF was significantly increased in S and L+F groups (P＜0.05).Compared with group S,the escape latency was significantly shortened at 3-7 days after operation in group L and at 5-7 days after operation in group L+F,and the expression of Wnt,p-GSK-3β and β-catenin was significantly up-regulated,and the concentrations of Aβ-42 and p-tau-181 in CSF were decreased in L and L+F groups (P＜0.05).Compared with group L,the escape latency was significantly prolonged at 3-6 days after operation,the expression of Wnt,p-GSK-3β and β-catenin was down-regulated,and the concentration of p-tau-181 in CSF was increased in group L+F (P＜ 0.05).Compared with group F,the escape latency was significantly shortened at 3-7 days after operation,the expression of Wnt,p-GSK-3β and β-catenin was up-regulated,and the concentrations of Aβ-42 and ptau-181 in CSF were decreased in group L+F (P＜0.05).Conclusion The mechanism by which lithium chloride preconditioning improves in postoperative cognitive function is partially related to activating Wnt/β-catenin signaling pathway in aged rats.