Objective To investigate the mechanisms underlying cognitive impairment induced by chronic aluminum exposure through observing the relationships between learning and memory functions and levels of ACh, β?EP, SOD, and MDA in the mouse cerebral cortex. Methods Mice were fed diets containing various doses of AlCl3. Their learning and memory abilities were measured by the Y maze test, and levels of ACh, β?EP, SOD, and MDA in the mouse cerebral cortex were measured at end of the experiment. Results The learning times and memory errors in groups administered moderate and high doses of aluminum were significantly increased compared with those in the control group. The levels of ACh, β?EP, and SOD in the cerebral cortex were decreased significantly, whereas the MDA level in the cerebral cortex was increased in groups administered moderate and high doses of aluminum compared with the control group. ACh, β?EP and SOD levels in the cerebral cortex were negatively correlated with learning times and memory errors in mice administered moderate and high doses of aluminum. MDA levels were positively correlated with learning times and memory errors in mice administered the high dose of aluminum. Conclusions Aluminum reduces the abilities of learning and memory in mice, possibly through decreasing the levels of ACh, β?EP, and SOD, and increasing the MDA level in the cerebral cortex, which may be the mechanisms underlying aluminum?induced cognitive impairment in mice.