Abstract: Objective To explore the effect of Wu-Ling Powde therapy on cognition, Aβ_1-42 and p-Tau expression in APP_swe/PS1_dE9 double transgenic AD mice. Methods Twenty APP_swe/PS1_dE9 double transgenic AD mice, half male and half female, were randomly divided into disease model group, Wu-Ling Powder group [at the dosage of 100 mg/(kg·d)]. Additionally,10 normal C57BL/6 mice (half male and half female) were used as the healthy control group. The disease model group and the healthy control group were given the same volume of normal distilled water,and the Wu-Ling Powder group was administrated by gavage for 30 days, respectively. All animals were fed normally.The behavioral tests such as Morris water maze test, place navigation test and probe trial testing were carried out in these groups. All the mice in three groups were killed in one hour after the last medication,hippocampus of these mice were separated for the detection of Aβ_1-42 and p-Tau by enzyme-linked immunosorbent assay (ELISA). Results ① Compared with the healthy control group, the latent period of the Wu-Ling Powder group in water maze test, target quadrant swimming time, effective zone residence time and platform times were increased significantly (all P<0.01); compared with the disease model group, the latent period in water maze test, target quadrant swimming time, effective zone residence time and platform times of the Wu-Ling Powder group were decreased significantly (all P<0.01). ② Compared with the healthy control group, the expression levels Aβ_1-42 and p-Tau in hippocampus of the Wu-Ling Powder group were increased significantly (all P<0.01); compared with the disease model group, the expression levels Aβ_1-42 in hippocampus of the Wu-Ling Powder group were decreased significantly (P<0.01). Conclusion Wu-Ling Powder has an effect on improving learning and memory ability, it may reduce the formation of Aβaggregates by decreasing the content of Aβ_1-42 in the hippocampus of mice, and thus reducing the generation of senile plaques.