OBJECTIVE：To study the regulatory effects of stilbene glucosid e（TSG）on c-Jun N-terminal kinase （JNK）and protein phosphortase 2B（PP2B）in APP/PS1/Tau transgenic dementia （3×Tg-AD）mice，and to explore its potential mechanism of anti-Alzheimer’s disease （AD）. METHODS ：Totally 45 male 3×Tg-AD mice were randomly divided into model group ，positive control group （huperzine A ，0.15 mg/kg），TSG low-dose ，medium-dose and high-dose groups （0.033，0.1，0.3 g/kg），with 9 mice in each group. Another 9 normal male C 57BL/6J mice were included into normal control group. Administration groups were given relevant medicine intragastrically ，once a day ，for consecutive 60 d. Normal control group and model group were given constant volume of normal saline intragastrically. After medication ，Morris water maze experiment was used to test the spatial learning and memory ability of mice in each group ；Nissl staining was used to observe the changes of Nissl bodies in cerebral cortex and hippocampus ；mRNA and protein expressions of JNK and PP 2B were detected by qRT-PCR and Western blotting assay. RESULTS：Compared with normal control group ，the escape latency was significantly prolonged （P＜0.01），the retention time of the original platform quadrant was significantly shortened （P＜ and the times of crossing the platform was significantly reduced in model group （P＜0.01）；the number of Nissl bodies in cerebral cortex and hippocampus was significantly 729011126@qq.com reduced，the staining was slight ；the relative expressions of JNK mRNA and protein were significantly increased （P＜ 0.01），and the relative expressi ons of PP 2B mRNA and protein were significantly decreased （P＜0.01）. Compared with model group ，the escape latency was significantly shortened in positive control group and TSG groups （P＜0.01）；the retention time of the original platform quadrant was significantly prolonged （P＜0.01）；the times of crossing the platform was significantly increased （P＜0.01）；the number of Nissl bodies in cerebral cortex and hippocampus was increased significantly ，the staining was heavy ；the relative expression of JNK protein was significantly decreased（P＜0.05 or P＜0.01），the relative expressions of PP 2B mRNA and protein were significantly increased （P＜0.01）， while the relative expression of JNK mRNA was significantly decreased in TSG high-dose group （P＜0.05）. CONCLUSIONS ：TSG can improve the learning and memory ability and neuronal damage of 3 × Tg-AD mice. The mechanism may be related to down-regulating the transcription and expression of protein kinase JNK ，up-regulating the transcription and expression of protein phosphatase PP 2B.