AIM: To investigate the mechanism of action of Tamarix chinensis Lour. on streptozotocin-induced type 2 diabetes mellitus (T2DM) through network pharmacology, molecular docking and experimental validation. METHODS: Using the TCSMP database and Swiss Target Prediction tools screen the active components and predict potential targets in Tamarix chinensis Lour.. Retrieving potential disease targets associated with T2DM from databases such as GeneCards, OMIM, and DisGeNET. The intersection targets of Tamarix chinensis Lour. and T2DM disease was obtained through Venny platform. The STRING database was used to constructed PPI network, and Cytoscape 3.8.0 software was use to visualized. GO function enrichment and KEGG pathway enrichment analysis were performed through the Metascape database. Docking of important target proteins and compounds was carried out by AutoDock software. SPF grade male rats were randomly divided into normal group, model group, MET group (88.5 mg/kg), TE high-dose (800 mg/kg) group, TE medium-dose (400 mg/kg) group and TE low-dose (200 mg/kg) group (n=10). High-fat and high sugar feed combined with low dose STZ (45 mg/kg) was used to induce T2DM rat model, and the rats were administered orally for 5 weeks. Fasting blood glucose( FBG),insulin（FINS）level and HOMA-IR index, biochemical indicators ［superoxide dismutase (SOD), malondialdehyde (MDA), glycosylated hemoglobin A1c (HbA1c) and inflammatory factor ［interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), vascular cell adhesion molecular (VCAM-1) levels of the rats were also observed; morphological changes of renal tissue was observe by HE staining. RESULTS: Based on the screening conditions of oral bioavailability (OB) ≥ 30% and drug like properties (DL) ≥ 0.18, a total of 19 main active ingredients with potential therapeutic effects on T2DM were screened from Tamarix chinensis Lour., including ergosta-5,24(28)-dien-3,7,16-triol, quercetin-3,3'-dimethyl ether, kaempferol, quercetin, and others. By analyzing the potential targets of Tamarix chinensis Lour. for treating T2DM, a total of 185 potential target genes were screened, including SRC, EGFR, HSP90AA1, AKT1, ESR1, H1F1A, TNF, PIK3R1, etc, involving cancer signaling pathways, insulin resistance, MAPK signaling pathways, PI3K Akt signaling pathways, etc. Molecular docking results showed that the binding energies were all less than -5.0 kcal/mol, indicating that a strong binding ability between the active ingredients screened by Tamarix chinensis Lour. and the potential targets for the treatment of T2DM. The animal experiment results showed that compared with the model group, the weight loss of rats in the MET and TE groups was slowed down, and the levels of FBG, FINS, MDA, HbA1c, IL-1β, TNF-α, VCAM-1, HOMA-IR index were reduced，the SOD level was increased，and the differences were statistically significant (P<0.05，P<0.01),Renal tissue cellular morphology also showed notable improvement. Most importantly, all these results demonstrating dose-dependent effects. CONCLUSION: Tamarix chinensis Lour. displays a significant therapeutic effect on T2DM through multi-component, multi-target, and multi-pathway synergistic actions to improve blood glucose levels. The findings of this study provide a theoretical basis for the clinical application of Tamarix chinensis Lour. in the treatment of T2DM.