OBJECTIVE： To observe the effects of stilbene glycosidec （TSG） on okadaic acid （OA）-induced Tau protein phosphorylation in NG108-15 cells， and to investigate the potential anti-Alzheimer’s disease （AD） mechanism of this compound. METHODS： AD model of NG108-15 cells was induced by OA. The survival rate of NG108-15 cells was observed by MTT assay after pretreated with low-dose， medium-dose and high-dose of TSG （50， 100， 200 μmol/L）. The apoptosis of NG108-15 cells was detected by AO/EB double fluorescence staining. The protein and mRNA expression of CDK5 and GSK3β， and the protein expression of Tau and p-Tau were detected by Western blotting assay and RT-PCR. The distribution of CDK5， GSK3β and Tau protein were detected by immunofluorescence. RESULTS： The normal morphology of NG108-15 cells was observed in normal control group， but CDK5， GSK3β and Tau protein were not found or few was found. Contracted or globular early apoptotic cells were observed in model gorup； the distribution of CDK5， GSK3β and Tau protein was increased， while survival rate of the cells was decreased； protein and mRNA expression of CDK5 and GSK3β as well as ratio of the relative expression of p-Tau to that of Tau （p-Tau/Tau） were all increased significantly （P＜0.05 or P＜0.01）. After pretreatment of TSG， the distribution of early apoptotic cells as well as CDK5， GSK3β and Tau protein were all decreased to some extent in administration groups， while survival rates of the cells were increased significantly. Protein expression of CDK5 and p-Tau/Tau in medium-dose group and high-dose group as well as mRNA expression of CDK5， protein and mRNA expression of GSK3β in administration group were decreased significantly （P＜0.05）. CONCLUSIONS： TSG can protect against AD model cells， the effects of which may be associated with improving survival rate of the cells， down-regulating the protein expression and gene transcription level of phosphokinase CDK5 and GSK3β， inhibiting Tau protein phosphorylation.