Objective To investigate the effect of 5-HT6 receptor antagonist SB-399885 on cognitive and memory impairment in rats with schizophrenia by blocking the HTR6/mTOR pathway. Methods A total of 40 SD rats were randomly divided into 4 groups： blank control group， schizophrenia model group （SZ group）， SZ+SB-399885 group （10 mg/kg）， positive control group （SZ + risperidone， 0.1 mg/kg）， with 10 rats in each group. The SZ rat model was established using MK-801. The new object discrimination experiment was used to detect the visual recognition memory of rats. The Morris water maze test was used to detect the cognitive ability of rats. The passive avoidance test was used to detect the learning and memory ability of rats. The AChE activity assay kit was used to detect the activity of AChE in hippocampus and cerebral cortex of rats. TUNEL staining method was used to detect the neuronal apoptosis in the hippocampal CA1 region of rats. Western blot was used to detect the expression of HTR6/mTOR pathway-related proteins in rat hippocampus. Results Both 5-HT6 receptor antagonists SB-399885 and risperidone could significantly improve visual recognition and memory impairment， cognitive impairment and learning and memory impairment in SZ rats （P＜ 0.05）. Compared with SZ group， the hippocampal AChE activity ［（0.008±0.001）μmol/（min·mg）］， the neuronal apoptosis rate （21.75±4.45） %， HTR6 protein expression （0.56±0.10） and mTOR activity （0.41±0.05） in the SZ + SB- 399885 group was significantly reduced （P＜ 0.05）. The AChE activity in hippocampus and cerebral cortex of positive control group rats was significantly reduced （P＜ 0.05）. The neuronal apoptosis rate （19.28±5.22）%， HTR6 protein expression （0.40±0.10）， and mTOR activity （0.33±0.05） were significant decreased （P＜ 0.05） in positive control group. Conclusions The 5-HT6 receptor antagonist SB-399885 may improve cognitive and memory impairment in schizophrenic rats by blocking the HTR6 / mTOR pathway.