To explore the mechanism of Radix et Rhizoma Rhei in the treatment of Alzheimer’s disease(AD) based on network pharmacology.The effective components and target genes of Radix et Rhizoma Rhei were screened by TCMSP database and Uniprot database.The target genes of AD were screened by Dragbank,Dis Ge NET and TTD databases.After mapping the component target with the disease target point,Cytoscape 3.7.1 software was used to construct the drug active component-target protein interaction network,and at the same time,the String database was used to draw the target protein-target protein interaction network;The target protein was analyzed by GO and KEGG using Metascape database.Finally,the main results of network pharmacology were verified by MTT,ELISA and real-time quantitative PCR.The research screened out that 17 active ingredients of Radix et Rhizoma Rhei,276 corresponding targets,included 107 targets related to AD,the top 10 KEGG-related signal pathways,and the first 20 biological processes for GO analysis.Cell experiment showed that Radix et Rhizoma Rhei effectively improved the cell survival rate of PC12 cells,inhibited the inflammation,apoptosis,oxidative stress of PC12 cells,and promoted the activation of PI3K/Akt/Nrf2/HO-1 signaling pathways,meanwhile,down-regulated NF-κB signaling pathway.Radix et Rhizoma Rhei has an important therapeutic effect on AD mainly through anti-inflammatory,anti-apoptotic and anti-oxidative stress.This provided new ideas for subsequent clinical treatment of AD.