This study aims to investigate the mechanism of liposoluble components of Artemisia integrifolia L. bud (AILC) in regulating type 2 diabetes melitus (T2DM) by using network pharmacology and experimental validation. Firstly, AILC was prepared and 24 compounds were isolated. The targets of AILC were obtained using the SwissTargetPrediction database; using GenCards, OMIM, and TTD databases to obtain T2DM disease targets. Then, analyze the relationship between the potential active ingredients, core targets, and pathways of AILC regulating T2DM through Venn, Cytoscape 3.10.1, String, and DAVID databases. And finally, experimental verification was conducted by establishing a T2DM rat model. Network pharmacology results indicate that AILC may act on key targets of T2DM, including protein kinase B, tumor necrosis factor, interleukin-6, vascular endothelial growth factor A(VEGFA), and peroxisome proliferator-activated receptor gamma. These targets are mainly enriched in the hypoxia-inducible factor-1 signaling pathway, phosphoinositide 3-kinase/protein kinase B signaling pathway, human cytomegalovirus infection, non-small cell lung cancer, and the relaxin signaling pathway. Animal experiments showed that AILC could significantly reduce the levels of total cholesterol cholesterol, triglycerides, and blood glucose in rat serum. Verification by immunohistochemistry and Western blot methods indicated that AILC significantly down regulated the expression of VEGFA in rats (P < 0.05). The aforementioned study indicated that the AILC regulated the expression of VEGFA protein and corrected dysregulated glucose and lipid metabolism, thereby exerting a therapeutic effect on T2DM.