〔Abstract〕 Objective To explore the effects of Blonanserin on hippocampal neurons damage and PI3 K/AKT/GSK3β signaling pathways in rats with MK-801 induced schizophrenia. Methods The schizophrenia models were induced by one-time intraperitoneal injection of MK-801. A total of 48 SD rats were randomly divided into normal group, model group, Blonanserin group(1 mg/kg Blonanserin) and risperidone group(0.54 mg/kg risperidone), with 12 cases in each group. The behaviors of rats were observed by stereotyped behavior assay, open field test and Morris water maze. The pathological damage of hippocampus was observed by HE staining, which was scored. The levels of serum glucose-lipid metabolism indexes were detected. The mRNA and proteins of phosphatidylinositol 3-kinase(PI3 K), protein kinase B(AKT) and glycogen synthase kinase 3β(GSK3β) in hippocampal tissues were detected by real-time fluorescent quantitative PCR and Western blot. Results Compared with model group, scores of stereotyped behaviors, total distance in open field test, escape latency and score of pathological damage in hippocampus decreased in Blonanserin group and risperidone group, while times of crossing platform original site, levels of PI3 K, AKT and GSK3β mRNA, and phosphorylation levels of PI3 K, AKT and GSK3 increased(P<0.05). However, there was no significant difference in the above indexes between Blonanserin group and risperidone group. The differences in levels of fasting blood glucose(FPG), glycosylated hemoglobin(HbA1 c), triglyceride(TG), total cholesterol(TC), high-density lipoprotein(HDL) and low-density lipoprotein(LDL) among normal group, model group and Blonanserin group was not statistically significant. However, levels of FPG, HbA1 c, TG and TC in risperidone group were higher than those in the other three groups(P<0.05), and there was no significant change in HDL or LDL. Conclusion Blonanserin may protect schizophrenia rats from hippocampal neurons damage, improve cognitive function, learning and memory ability by activating PI3 K/AKT/GSK3β signaling pathways.