Abstract： Objective： To explore the toxicological mechanism of adrenal insufficiency induced by Tripterygium wilfordii based on network pharmacology and molecular docking technology. Methods： The candidate core toxic compounds and main targets of Tripterygium wilfordii were collected through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and PharmMapper， and the potential toxic targets of adrenal insufficiency were collected in Comparative Toxicogenomics Database (CTD). After the intersection of the two，STRING database was used to analyze the toxic target genes of Tripterygium wilfordii-induced adrenal insufficiency. The protein-protein interaction (PPI) network was constructed by using Cytascape software，and the core genes were identified by using the cytoHubba plug- in according to the MCC score. In addition，DAVID database was used to enrich and analyze the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) of the toxic target gene of Tripterygium wilfordii-induced adrenal insufficiency. Molecular docking verification of core toxic compounds and core genes was carried out through Auto Dock Vina 1.2.2. Results ： A total of 8 candidate toxic compounds of Tripterygium wilfordii and 133 potential toxic targets of adrenal insufficiency were obtained. The results of network analysis showed that nobiletin， stigmasterol， triptonide， isoxanthohumol and triptolide might be the main compounds of Tripterygium wilfordii- induced adrenal insufficiency toxicity. The top 10 genes of adrenal insufficiency toxicity in MCC score were CASP3， HSP90AA1，ALB，SRC，EGFR，ESR1，MAPK1，AR，PGR and MAPK8. GO and KEGG analysis showed that Tripterygium wilfordii caused adrenal insufficiency through biological processes such as protein hydrolysis， protein self- phosphorylation， apoptosis， protein phosphorylation， cell components such as cell fluid， extracellular secretion， cytoplasm， steroid binding， zinc ion binding， peptidase activity and other molecular functions. Through tumor pathway， lipid and atherosclerosis， MAPK signaling pathway， reactive oxygen species， receptor activation and other pathways， adrenal function is reduced. Molecular docking showed that the two core toxic compounds and three core toxic targets of Tripterygium wilfordii were highly stable. Conclusion： The toxicological effect of Tripterygium wilfordii on adrenal insufficiency may be caused by Tripterygium wilfordii toxic compounds acting on 133 core targets and 107 signal pathways.