AIM: To explore the mechanism of the action of 2,3,5,4′- tetrahydroxystilbene-2-o-β-D-glucoside (TSG) on mimetic dementia mice. METHODS: Three months old mice were divided into three groups: control (saline sc and ig) , D-galactose (50 mg · kg -1 · d -1 sc) plus saline (ig), and D-galactose (50 mg · kg -1 · d -1 sc) plus TSG (0.1 g · kg -1 · d -1 ig). After treatment for 60 d, each group of six mice was tested by Morris water maze and the total RNA of each group's hippocampal tissue in equiponderant weight were isolated by TRIZOL agent. The mRNA of control group was reversely transcribed to cDNA by using Cy5-dUTP, while mRNA of D-galactose and TSG group was reversely transcribed by using Cy3-dUTP. The mixture of control and D-galactose group cDNA probes were hybridized with gene chip consisted of 4000 genes, and the mixture of control and TSG group cDNA probes were hybridized with the the same kind of gene chip. The fluorescent signals of gene chip were analyzed by GenePixPro 3.0 system. RESULTS: Compared with the D-galactose group, the expression of 41 genes from TSG group varied differently and seemed to trend to that of control group. Among 41 genes, 29 genes were up-regulated and 12 genes were down-regulated. CONCLUSION: Mer the intervention of TSG, some genes' expression in mouse hippocampus seemed to be improved. These genes are related to energy metabolizing, inflammatory reaction, nerve growth-related factors and total genes transcription level.