Abstract: OBJECTIVE To explore the mechanism of treating Alzheimer's disease model mice by Xiusanzhen. METHODS APP/PS1 transgenic mice were taken as AD animal model and randomly divided into model group， Xiusanzhen group， Xiusanzhen with olfactory nerve transected group and Donepezil HCl group， negative mice were taken as control group and sham group. Xiusanzhen group and Xiusanzhen with olfactory nerve transected group had electric-acupuncture at Yintang （EX-HN3）and Yingxiang (LI20) acupoints. Donepezil HCl group had gastric perfusion with Donepezil HCl.Y maze was used to observe cognitive function of mice. Immunohistochemistry and Western Blot were used to determine the protein expression of Aβ， p-JNK， p-ERK1/2， p-Tau (Ser 396) in hippocampus of mice. RESULTS Xiusanzhen group significantly improved cognitive function(P<0.05); protein expression of Aβ， p-JNK， p-ERK1/2， p-Tau (Ser 396) protein in the model group was significantly higher than the others， while significantly reduced after Xiusanzhen and Donepezil HCl treatment; however， was no significant change and statistical significance after Xiusanzhen with olfactory nerve transected treatment (P>0.05). CONCLUSION Xiusanzhen can regulate protein expression of Aβ， p-JNK， p-ERK1/2， p-Tau (Ser 396) and improve the cognitive function of AD mice， meanwhile， the integrity of the olfactory pathway is the way to play the theraputic effect.