Abstract: Objective To study the role of N-methyl-D-asparate (NMDA) receptor in the damage of learning and memory induced by sub-chronic aluminum exposure in rats.Methods Thirty-six healthy male adult Sprague-Dawley (SD) rats were randomly divided into normal saline,low,moderate,and high dose aluminium exposure group(0.41,0.81,and 1.23 mg/kg·w).The rats were exposed to Al(mal)₃ with intraperitoneal injection for 8 weeks.After the exposure,Morris water maze test was performed to test the learning and memory abilities of the rats.Hematoxylin-eosin staining (HE) staining was employed to observe pathologic changes of hippocampus.The expression of NMDA receptor in moderate and hippocampus was detected with western blot.Results The time of platform-finding was prolonged for the rats in moderate and high dose exposure group (44.12±5.62 s,45.95±13.97 s) compared to that of rats in low dose exposure group(29.86±10.34s)(P<0.05).The dispersed arrangement,decreased cell nnmber,nuclei atrophy,and vacular degeration were observed in hipocapal pyramida cells of the rats with high dose aluminum exposure.Compare to that of the normal saline group,NMDAR receptor 2A protein of the rats in moderate(0.44±0.12) and high dose exposure group (0.32±0.19)was significantly decreased (P<0.05) in a dose-response manner.Compare to that of the control group,the expression of NMDA receptor-2B subunits protein was not significantly different in aluminum exposure groups.Conclusion Sub-chronic aluminum exposure could induce learning and memory damage in rats and its mechanisms may be associated with the chancg of NMDAR subunits protein expression.