To investigate the effect and mechanism of paeonia lactiflora extract on the cognitive function of high-fat diet induced rats so as to provide new ideas for clinical treatment of cognitive dysfunction in schizophrenia. Methods:A total of 40 male SD rats were feed with high-fat and high-glucose diet, and they were divided into a blank control group, a model control group, a metformin group, a paeonia lactiflora extract group with 10 cases in each group. The 10 rats were respectively orally given with normal saline, 0.15 g/kg metformin solution, 5 mg/mL paeonia lactiflora extract. After the administration, the rats' body weight, gonadal fat mass, blood glucose and glycosylated hemoglobin were measured. The Morris water maze system was used to measure the cognitive function of rats in each group, and the protein expression levels of PI3K and AKT were measured by Western blotting. Results:Compared with the model control group, the weight, body weight, gonadal fat mass, blood sugar and glycosylated hemoglobin of rats in the metformin group and the peony extract experimental group were reduced (P<0.05); the escape latency and exploration distance of rats were significantly reduced, and the target quadrant swimming time increased significantly and the number of platform crossings increased significantly; the expression levels of PI3K and phospho-AKT (S473) proteins in the hippocampus of rats decreased. Conclusion:Paeonia lactiflora extract can reduce the body weight and blood glucose levels in high-fat diet induced rats, and improve their cognitive function. The mechanism is related to the inhibition of the PI3K/AKT signaling pathway. Paeonia lactiflora extract may be a new way for the treatment of cognitive dysfunction in schizophrenia.