Objective To investigate the mechanism of action of memantine in vascular dementia by studying the change of N-methyl-D-aspartate-2B receptor(NMDAR-2B) in hippocampus of vascular dementia rats.Methods 128 Wistar rats were randomly divided into sham operation group,vascular dementia(VaD) model group and memantine groups treated with high or low dose.Eight rats of each group were sacrificed at 4,8,12,16 weeks post operation.The water maze test was performed to examine the ability of learning and memory of the rats and the expression of NMDAR-2B in hippocampus was measured by immunohistochemical staining.Results The ability of learning and memory of VaD rats decreased significantly compared with the sham rats.The expression of NMDAR-2B in VaD rats increased greatly first then fell down and was significantly different from that of the sham group.At 4 weeks post operation,both memantine-treated groups presented no statistical difference in learning and memory level and the expression of NMDAR-2B compared with the sham group.However,at 8,12,16 weeks post operation,the above two indexes of high-dose group were better than those of VaD rats,but still worse than those of the sham group.Conclusion The change of NMDAR-2B was related to the impairment of learning and memory of VaD rats and memantine at adequate dosage improved recognition function by modulating NMDAR-2B.