Abstract: Objective To investigate the role of mTOR signaling pathway in learning and memory dysfunction in mice with neuroinflammation. Methods One hundred and eight C57 mice were randomly divided into control group (Nctrl group, n=36), solution control group (Sham group, n=36), and intraventricular injection of LPS group (LPS group, n=36). Mice in LPS group received intracerebroventricular injection of 2000ng LPS, sham group received intracerebroventricular injection of equivalent artificial cerebrospinal fluid, Nctrl group did not receive any treatment. At d1, d2, d3, 6 rats of each group were given contextual fear condition (CFC) test to detect learning and memory function and other 6 rats were sacrificed to collect hippocampal tissue, IL-1β, TNF-α, Aβ were measured by ELISA and p-mTOR, p-P70S6K, p-Tau were measured by western blot. Another 48 C57 mice were randomly divided into control group (Ctrl group, n=12), rapamycin control group (ctrl+RAPA group, n=12), intraventricular injection of LPS group (LPS group, n=12), and rapamycin group (LPS+RAPA group, n=12). Mice in LPS group and LPS+RAPA group received intracerebroventricular injection of 2 000 ng LPS, Ctrl+RAPA group and LPS+RAPA group were intraperitoneally injected of rapamycin at 0.5 mg/(kg · day) for 3 days before LPS intracerebroventricular injection. CFC, IL-1 β, TNF- α, p-mTOR, p-P70S6K, p-Tau, Aβ were measured with the same methods mentioned above. Results At d1 and d2 after injection, compared with Nctrl group, freezing time ratio in mice of LPS group decreased (d1:43.80%±5.27% vs 66.42%±5.52%; d2:53.35%±4.43% vs 66.17%±5.79%; P < 0.05 respectively), while, TNF-αd1:(26.33±2.27) pg/ml vs (14.68±0.76) pg/ml; d2:(21.16±2.18) pg/ml vs (15.11±1.09) pg/ml and IL-1βd1:(27.36±2.53) pg/ml vs (17.49±1.18) pg/ml; d2:(22.58±1.87) pg/ml vs (17.04±1.37) pg/ml increased in the hippocampus (P < 0.05 respectively); p-mTOR (d1:2.54±0.14 vs 1.41±0.14; d2:2.06±0.13 vs 1.39±0.08), p-P70S6K (d1:0.77±0.08 vs 0.46±0.06; d2:0.68±0.06 vs 0.45±0.05), p-Tau (d1:1.34±0.13 vs 0.38±0.03; d2:1.21±0.16 vs 0.39±0.04) and Tau protein (d1:3.29±0.23 vs 1.96±0.11; d2:2.61±0.21 vs 1.96±0.07) increased in the hippocampus in mice of LPS group (all P < 0.05). In the mTOR experiment, compared with LPS group, freezing time ratio in mice of LPS+RAPA group increased (52.78%±3.57% vs 42.13%±2.93%, P < 0.05), while TNF-α(18.98±2.07) pg/ml vs (27.17±1.72) pg/ml, IL- 1β(18.28±1.67) pg/ml vs (28.78±2.57) pg/ml decreased in the hippocampus (P < 0.05 respectively), p-mTOR (1.67±0.11 vs 2.45±0.18), p-P70S6K (0.65±0.05 vs 0.79 ±0.06), p-Tau (0.56±0.07 vs 1.38±0.08) and Tau protein (2.17±0.18 vs 3.27±0.22) decreased in the hippocampus of mice in LPS+RAPA group (all P < 0.05). Conclusion mTOR signaling pathway is involved in learning and memory dysfunction of neuroinflammation mice.