The objective of this study is to determine the effects of Pb 2+ on N-methyl-d-aspartate receptor (NMDAR) subunits—NR1C1, NR2A and NR2B in primary cultured neuronal cells. We hypothesize that l-glutamic acid (GA) reverses Pb 2+ -induced NMDAR damage. Neuronal cells were isolated from the fetus brain at 18–20th day of gestation of pregnant Sprague Dawley (SD) rats. All experiments were included three independent cell preparations (N=3). The neuronal cells were exposed to Pb 2+ (10 −10 , 10 −9 , 10 −8 and 10 −7 M) for 24h. Neurons were pretreated with NMDAR agonist—l-glutamic acid (GA) (200μM) and antagonists dizocipine (MK-801, 50nM) for 1h and then exposed to 10 −7 M of Pb 2+ for 24h. Finally, GA at 2, 0.2 and 0.02mM was incubated with neurons prior to Pb 2+ exposure. Aliquots of NR1, NR2A and NR2B proteins from cell homogenate were immunoprecipitated with protein A agarose and detected by Western blotting. The addition of GA unconventionally reversed the reductions of NMDAR by Pb at protein levels, whereas MK-801 exacerbated Pb 2+ -induced damage. The protection by GA against Pb 2+ -induced reduction of NMDAR was dose-dependent. These findings suggest that the administration of GA may be a potential approach to intervene the Pb 2+ -induced NMDAR alterations.