Abstract: Objective To investigate the changes in the expressions of p53, DKK (the inhibitor of Wnt pathway) and phosphorylated tau in rat bilateral hippocampus after β-amyloid peptide (β-AP) (25-35) injection, and observe the effect of saponin B from Anemarrhena asphodeloides Bunge (SAaB) in this model. Methods After bilateral injection of β-AP (25-35) into the hippocampus of rats, RT-PCR was performed for observing the changes in p53 and DKK mRNA expressions and immunochemistry carried out to detect the changes in phosphorylated tau protein. Results RT-PCR showed increased p53 and DKK mRNA expression and immunochemistry revealed increased phosphorylated tau-positive cells in rat hippocampus after β-AP (25-35) injection, and administration of SAaB significantly ameliorated these changes. Conclusion SAaB can significantly ameliorate β-AP-induced tau hyperphosphorylation by inhibiting increased p53 and DKK mRNA expressions in response to β-AP injection.