Abstract: Objective To observe the effect of Huoxue-Yizhi tablet on brain N-methyl-D-aspatric acid receptor(NMDAR) expression and the contents of nitric oxide(NO) and 5-hydroxy trypotamince(5-HT), and to explore protective mechanism of the tablet.Methods Repeated ischemia reperfusion was used to establish vascular dementia(VD)model in rats with oral administration of Huoxue-Yizhi tablet for 28 days.Learning and memory ability of the rats were tested using Morris water maze.The expression of NMDAR in brain tissue was determined with immunohistochemistry;5-HT content in cerebral tissue was measured with liquid chromatography-mass spectrometry and NO content was determined with nitrate reductase method.Results Compared with the control group, the escape latency(34.11±13.58 s) in model group was significantly longer;the content of 5-HT(20.26±0.57 ng/g)was decreased and the NO content(132.61±33.99 μmol/gprot) was increased;the expression of NMDAR was downregulated.Compared with the model group, the escape latercy(15.18±6.82 s) was significantly shortened;the content of brain 5-HT(26.23±3.08 ng/g) was increased;and NO content(95.57±29.06 μmol/gprot) and NMADR expression was decreased(P<0.05) in the rats with high-dose(6.20 g/kg) Huoxue-Yizhi tablet treatment.Conclusion Huoxue-Yizhi tablet can obviously improve the behavior of vascular dementia rats, and the effect might be related to the increased NO and 5-HT and decreased NMDAR expression in the brain of the rats.