Abstract: This study is to explore the effect of ginsenoside Rb1 on the process of β-amyloid peptide_25-35 (Aβ_25-35)-induced hyperphosphorylation of tau protein ,and on the level of cyclin-dependent kinase 5 activator, p25/p35. Western blotting and/or immunocytochemical staining were used to detect the levels of phosphorylation of tau protein at the sites of Thr²⁰⁵, Ser³⁹⁶, Ser⁴⁰⁴ in hippocampal neurons , cdk5 and p25/p35. After exposure to Aβ_25-35 (20 μmol·L^-1) for 12 h, the levels of tau protein phosphorylation at the sites of Thr²⁰⁵, Ser³⁹⁶, Ser⁴⁰⁴ were enhanced, the level of p25 was increased, but the level of protein cdk5 was not changed markedly. Pretreatment with ginsenoside Rb1 reduced Aβ_25-35-induced hyperphosphorylation of tau protein and decreased the lever of p25, but had no effect on cdk5. Ginsenoside Rb1 can attenuate Aβ_25-35-induced hyperphosphorylation of tau protein through CDK5 signal pathway.