Abstract: Objective To investigate whether rapamycin reduces deposition of p-tau protein induced by aluminum through mTOR inhibiton. Methods The study employed four groups of 24 SD rats: control, low dose aluminum maltol(10 μmol/ kg Al(mal)3), medium dose aluminum maltol(20 μmol/ kg Al(mal)3 ), and high dose aluminum maltol(40 μmol/ kg Al(mal)3), groups. The Morris water maze (MWM) test was used to assess the learning and memory abilities of rats. p-tau, p-mTOR, and PSD95 in the hippocampus were detected by Western blot. PC12 cells were divided into control, aluminum treatment, aluminum+DMSO, aluminum+100 nmol rapamycin, aluminum+300 nmol rapamycin, and divided into Al-treated and Al+rapamycin groups, the MWM test was used to assess learning and memory abilities of rats. p-tau, p-mTOR, and PSD95 in the hippocampus were detected by Western blot. Results The MWM test showed that the escape latency time of rats in the aluminum-treated group was longer than that in the control group, and that in medium and high dose aluminum mal groups was significantly longer than that in the control group ((35. 24±4. 78) and (25. 92±8. 80)vs (20. 32±6. 04), P<0. 001). The target quadrant residence time and crossing platform times of rats in Al exposure groups were decreased with the increase in the Al exposure dose (P<0. 05). Compared with the findings in the control group, in the aluminum-treated group, p-mTOR/ mTOR and p-tau/ tau levels in the hippocampus of rats were significantly increased (P<0. 05), and PSD95 was significantly decreased (P<0. 05). Compared with the findings in the group exposed to aluminum alone, in rapamycin treatment groups, p-mTOR/ mTOR and p-tau/ tau were decreased, especially in 300 and 500 nmol rapamycin groups, p-tau was restored to the normal level of the control group, and PSD95 was also increased significantly (P<0. 05). Compared with the findings in Al-treated groups, in Al+rapamycin group, learning and memory abilities of rats were improved, p-mTOR/ mTOR and p-tau/ tau in the hippocampus of rats were significantly decreased (P<0. 05), and PSD95 was significantly increased (P<0. 05). Conclusions Activation of mTOR phosphorylation is involved in excessive deposition of p-tau protein induced by aluminum. Rapamycin inhibits p-tau deposition by inhibiting the phosphorylation activity of mTOR.