Intravenous therapy often triggers phlebitis as an adverse effect, and there are limitations in modern medical treatments. The aim of this study was to investigate the mechanism of action of Qufushengji hydrogel, a novel topical preparation of traditional Chinese medicine, in the treatment of phlebitis. Based on network pharmacology and molecular docking technology, we screened the active ingredients (criteria: relative molecular weight molecular weight ≤500 Da, drug-likeness DL ≥0.18) from 4 Chinese medicines (e.g., Panax ginseng, Resina Draconis) contained in the hydrogel and combined them with the GeneCards database to obtain phlebitis-related targets. We predicted transdermal permeability by the Potts-Guy model, constructed protein–protein interaction networks and drug-component-target-disease networks, and conducted gene ontology/KEGG pathway enrichment analysis and molecular docking validation. A total of 90 active ingredients and 221 potential targets were screened, and 21 key targets were obtained after taking the intersection with phlebitis-related targets. Abietic acid, dehydroabietic acid, and oleanolic acid were identified as the core active ingredients, and IL-10, TNF, IL-6, VCAM1, and ICAM1 were identified as the core targets. Enrichment analysis indicated that Qufushengji hydrogel may intervene in immune-inflammatory responses, metabolic complications, and pathogen infection-related mechanisms by modulating AGE-RAGE, TNF, and other pathways. This study reveals the potential mechanism of Qufushengji hydrogel in treating phlebitis through the “multi-component-multi-target-multi-pathway” model, which provides a theoretical basis for the treatment of phlebitis by traditional Chinese medicine.
