OBJECTIVE：To study the e ffects of stilbene glycoside c（TSG）on phosphorylation of Thr 205，Ser404 sites of Tau protein in Aizheimer ’s disease （AD）model mice ，and to investigate the potential anti-AD mechanism of TSG. METHODS ：APP/ PS1/Tau three transgenes （3×Tg-AD）mice were randomly divided into model group ，positive control group （huperzine，0.15 mg/kg），TSG low-dose ，medium-dose and high-dose groups （0.033，0.1，0.3 g/kg），with 6 mice in each group. In addition ，6 C57BL/6J mice were chosen as normal control group. Administration groups were given relevant medicine intragastrically. Model group and normal control group were given equal volume of normal saline intragastrically ，once a day ，for consecutive 60 days. After last medication ，immunofluorescence staining was used to detect Tau protein and phosphorylated Tau protein （Thr205， Ser404 sites） distribution and expression in brain tissue of mice in each group. Western blotting assay was used to detect phosphorylated Tau protein （Thr205，Ser404 sites）expression level in brain tissue of mice in each group. RESULTS ：Compared with normal control group ，the expression of Tau protein，phosphorylated Tau protein （Thr205，Ser404 sites）in 729011126@qq.com the brain tissue of mice were increased in model group ，which were easy to aggregate and distributed more widely ；theirrelative expression were increased significantly （P＜0.01）. Results of Western blotting assay showed that the expression levels of phosphorylat ed Tau protein （Thr205，Ser404 sites）were increased significantly （P＜0.01）. Compared with model group ，the expression of Tau protein ，phosphorylated Tau protein （Thr205，Ser404 sites） in the brain tissue of mice were decreased in positive control group and TSG groups ；aggregation decreased，distribution narrowed and their relative expression were decreased significantly （P＜0.01）. Results of Western blotting assay showed that the expression levels of phosphorylated Tau protein （Thr205，Ser404 sites）were decreased significantly （P＜ 0.01）. Compared with positive control group ，There was no significant difference in the distribution of Tau protein ，phosphorylated Tau protein （Thr205，Ser404 sites）in the brain tissue of mice in TSG groups ；the relative expression were not statistically significant（P＞0.05）；but Western blotting assay showed the expression levels of phosphorylated Tau protein （Thr205 site）in TSG medium-dose and high-dose groups as well as the expression levels of phosphorylated Tau protein （Ser404 site）in TSG groups were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：TSG can play an anti-AD effect on AD model mice by down-regulating the expression of phosphorylated Tau protein （Thr205，Ser404 sites）in brain tissue.