Objective：To explore the neuroprotective effect of lovastatin(LOV)on N - methyl - D - aspartate(NMDA)induced excitotoxicity and the potential mechanism of LOV in regulating the function of NMDA receptors in neuroprotection. Methods：The primary cultured rat neurons were divided into the vehicle group，LOV group，NMDA group，LOV + NMDA group，glutamate(Glu) group and Glu + APV(a specific NMDA receptor antagonist)group. Neuronal morphology was detected by immunofluorescence staining，neuronal apoptosis was detected by TUNEL analysis，protein levels were detected by Western blotting，cell surface receptors were detected by biotinylation. Results：①Compared with the few surviving microtubule-associated protein 2(MAP-2)positive neurons in the NMDA group or the Glu group，the number of MAP -2 immunopositive neurons in the LOV+NMDA group and the Glu+APV group was significantly increased，as well as the number and length of neuronal dendrites were significantly increased(P ＜ 0.001). ②Compared with the significantly increased TUNEL-positive cells in the NMDA group or the Glu group，the TUNEL-positive cells in the LOV +NMDA group or the Glu +APV group were significantly decreased(P ＜ 0.001). ③Compared with the vehicle group，the expression of N - methyl - D - aspartate receptor(NR2B)in the NMDA group was significantly decreased(P ＜ 0.001)，while LOV pretreatment could increase the expression of NR2B when compared with the NMDA group(P ＜ 0.05). ④The cell surface receptor biotinylation assay showed that NMDA treatment resulted in the loss of the most NR2B on the cell surface(P ＜ 0.001)，while LOV pretreatment could significantly reduce the NMDA-induced loss of NR2B(P ＜ 0.05). Further studies showed that phosphorylation of NR2B at tyrosine(Tyr)1472 was decreased after NMDA treatment(P ＜ 0.05)，while pretreatment with LOV significantly restored the phosphorylation of Tyr1472(P ＜ 0.05). Conclusion：LOV may significantly attenuate the excitotoxicity induced by NMDA，and its neuroprotective effect is probably related to the selective regulation of NR2B surface expression by affecting the intracellular endocytosis and/or intracellular degradation of NR2B.