Clinical reports have demonstrated that the Kongsheng Zhenzhong pill (KSZZP), a classical prescriptionderiving from Valuable Prescription for Emergencies, has good therapeutic effects on vascular dementia. However, the mechanisms that mediate its effects remain unclear. In this study,the expression of N-methyl-D-aspartate receptor 1 mRNA, the content of nitric oxide, and the concentrationof calcium in neurons was determined with in situ hybridization, spectrophotometry and flow cytometry, respectively. In addition, the expressions of N-methyl-D-aspartate receptor 1, nervegrowth factor protein, and glial cell line-derived neurotrophic factor protein w ere detected with immunohis tochemistry.We found that KSZZP could significantly decrease the expression of N-methyl-D-aspartate receptor 1 mRNA and protein, the content of nitric oxide, and the concentration of calcium in neurons. KSZZP also increased the expression of nerve growth factor and glialcell line-derived neurotrophic factor protein in the hippocampus CA1 region and in the cerebralcortex. Morris water maze and passive avoidance tests verified that KSZZP ameliorated the cognitiveimpairments of vascular dementia rats. Moreover, the KSZZP-induced improvements in thecognitive functions of vascular dementia rats were correlated with both inhibition of N-methyl-D-aspartate-induced excitable neurotoxicity and elevation of neurotrophic factor expression.