Abstract：Objective：To explore the mechanism of action of Tongsai Granules (TSG) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) based on network pharmacology， molecular docking technology， and animal experiments. Methods： ① Predictive analysis. The active ingredients and corresponding targets of TSG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. AECOPD-related genes were retrieved by GeneCards， OMIM， and other databases. Venn diagrams were drawn to obtain intersecting drug-disease targets； active ingredient of TSG-intersecting target network and a protein-protein interaction network was constructed and core targets were screened out based on network relationships；R programming language software was used for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking of key active ingredients of TSG and core targets was performed by using AutoDockTool 1.5.6 software. ②Experimental verification. Fifty rats were randomly divided into control group, model group, Chinese medicine group, western medicine group, and combination group, with 10 rats in each group. The AECOPD rat model was constructed in all groups except the control group. And received drug gavage 2 days before and 4 days after the acute exacerbation. After treatment， the lung function indicators，including forced expiratory volume in 0.3 seconds (FEV0.3)，force vital capacity (FVC)，the ratio of forced expiratory volume in 0.3 seconds to forced vital capacity (FEV0.3 /FVC)，and peak expiratory flow (PEF)， were measured in each group. The contents of tumor necrosis factor (TNF) - α and interleukin (IL) - 7 in serum were measured； the pathological changes in airway and lung tissues were observed by using hematoxylin-eosin (HE) staining and the network pharmacological prediction results were validated by western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). Results： In the treatment of AECOPD，the key active ingredients of TSG were quercetin，apigenin，luteolin，kaempferol， and β - sitosterol， which mainly act on tumor suppressor protein 53 (TP53)， mitogen-activated protein kinase 3 (MAPK3)， and other core targets. GO and KEGG analyses showed that in AECOPD treatment， TSG was related to TNF， IL-17， and other signaling pathways related to intervening oxidative stress， reducing apoptosis， and inhibiting inflammation. Molecular docking analysis showed that the key ingredients of TSG had good binding activity to core targets for the treatment of AECOPD. The results of animal experimental research showed that the FVC， FEV0.3， FEV0.3 / FVC， and PEF values in the model group were all lower than those in the control group (P＜0.05). The FVC， FEV0.3， and PEF values in the Chinese medicine group， western medicine group， and combination group were all higher than those in the model group (P＜0.05). The FEV0.3/FVC value in the combination group was higher than that in the model group (P＜0.05). There were no significant differences in FVC， FEV0.3， FEV0.3 / FVC， and PEF values between the Chinese medicine group and the western medicine group (P＞0.05). The FVC and PEF values in the combination group were higher than those in the Chinese medicine group and the western medicine group (P＜0.05)； the FEV0.3 in the combination group was higher than that in the western medicine group (P＜0.05). The levels of TNF-α and IL-17 in serum in the model group were significantly higher than those in the control group (P＜0.05). The levels of TNF-α and IL-17 in the Chinese medicine group，the western medicine group，and the combination group were all significantly lower than those in the model group (P＜ 0.05). The levels of TNF - α and IL-17 in the serum in the combination group were lower than those in the Chinese medicine group and the western medicine group (P＜0.05). The protein expression levels of P-P65/ P65，P-AKT/AKT，P-MAPK1/3/MAPK1/3，and TP53/GAPDH in the lung tissue in the model group were higher than those in the control group (P＜0.05). The expression levels of the above proteins in the Chinese medicine group，the western medicine group，and the combination group were all lower than those in the model group (P＜0.05). The expression levels of the above proteins in the combination group were lower than those in the Chinese medicine group and the western medicine group (P＜0.05). Conclusion：TSG has the characteristics of multiple components，multiple targets，multiple pathways，and general regulation in the treatment of AECOPD，providing data support for further in-depth research.