To observe the effect of electroacupuncture on the level of P-glycoprotein and brain interstitial fluid Aβ in hippocampus in APP/PS1 transgenic mice, and to explore the mechanism of electroacupuncture in the treatment of Alzheimer's disease. Methods:Twelve male APP/PS1 transgenic mice were divided into electroacupuncture group and model group randomly. Six male C57BL mice were used as normal control group. The level of Aβ in the interstitial fluid of mice was detected by Elisa method after two weeks of electroacupuncture at Baihui (DU 20) and Yongquan (KI 1). The expression of P-glycoprotein in hippocampus was observed by immunohistochemistry. Results:Immunohistochemical results showed that the expression of P-glycoprotein was significantly decreased (P<001) in the model group when compared with the normal control group, and the expression of P-glycoprotein in the EA group was significantly increased (P<005) compared with the model group. ELISA test showed that the level of brain interstitial fluid Aβ in the model group was lower (P<001) than the level in the control group significantly. Compared with the model group, the level of Aβ in the acupuncture group was significantly decreased (P<001). Conclusion:Electroacupuncture can decrease the level of brain interstitial fluid Aβ and increase the expression of P-glycoprotein in hippocampus, which may explain why the EA have effects on AD.