This present investigation uses high throughput serum metabolomics and network pharmacology techniques to explore the pharmacological mechanism of Erzhi Pill in treating Alzheimer′s disease.Sixty male SD rats were randomly divided into 6 groups according to their body weight,with 10 in each group,namely,sham operation group,model group,positive drug group,low dose group,and medium dose combined high dose group.Rats in the model group and each administration group were given intraperitoneal injection of D-galactose and bilateral intraventricular injection β amyloid protein 25-35 (Aβ_25-35) to establish a rat model of Alzheimer′s disease.After the sixth week of model preparation,the medication group was given corresponding drugs for intervention every day,while the other groups were given the same volume of physiological saline (4 weeks).The spatial learning and memory abilities of rats in each group were observed using Morris water maze experiment,and the expression of tau protein in the hippocampus of rats was detected using Western blotting.Using high throughput serum metabolomics technology combined with pattern recognition methods to search for endogenous differential metabolites and related metabolic pathways;Using network pharmacology technology to explore the potential active ingredients and key targets of Erzhi Pills,further integrating metabolomics and network pharmacology technology to focus on key targets and components,and ultimately adopting molecular biology technology for targeted verification.The water maze experiment and the degree of tau protein in the hippocampus of rats proved that the model was successfully prepared.The metabolomics results showed that the metabolic profile of the model group and the sham operation group was significantly separated,and the administration group was between the sham operation group and the model group,which demonstrated that the overall metabolism of the model group rats had significant changes,and there was a trend of regression after administration of Erzhi Pill.The results of metabolomics revealed 16 biomarkers,mainly involving 10 metabolic pathways.The results of network pharmacology show that Erzhi Pill mainly contains 13 compounds including β-sitosterol,kaempferol,etc.and 11 protein components such as the toxic muscarinic acetylcholine receptor M1,a direct target associated with Alzheimer′s disease.Based on the above,it can be seen that Erzhi Pill has a good intervention effect on Alzheimer′s disease rats,which may achieve the purpose of intervention through the direct regulation of quercetin on cathepsin D.