ObjectiveTo observe the clinical effect of Liyin Decoction combined with Fengsui Decoction for the treatment of chronic pharyngitis in spleen and stomach deficiency with cold manifestation, and to explore its potential mechanism based on network pharmacology method. Methods(1) A total of 100 patients with chronic pharyngitis in spleen and stomach deficiency with cold manifestation were randomly divided into observation group or control group, with 50 cases in each group. Patients in the observation group received Liyin Decoction combined with Fengsui Decoction for treatment, while the control group was orally administrated Houyanqing Oral Liquid for treatment. The two groups were treated for 2 weeks. The post-treatment clinical efficacy, and pre- and post-treatment Traditional Chinese Medicine syndromes scores, serum interleukin (IL)-6 level, IL-10 level, tumor necrosis factor (TNF)-α level were compared between the two groups. (2) The active pharmaceutical components of Liyin Decoction and Fengsui Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the effect targets of the active components were screened from the databases of PharmMapper, Guided Database of Traditional Chinese Medicine, and UnitProt. After obtaining targets related to chronic pharyngitis through the databases of GeneCardsand OMIM, the intersection between the targets as above and the effect targets of active components was acquired. The protein-protein interaction network of intersection targets was established by the STRING database, after that the core targets were screened by employing the Cytoscape 3.9.1 software. The DAVID 6.7 database was used to perform enrichment analyses on the core targets. Results(1) The total effective rate of the observation group was higher than that of the control group (P<0.05). After treatment, the scores of dry and itchy pharyngeal, irritable cough, pharyngeal mucosa status, and serum IL-6, TNF-α levels were decreased, whereas serum IL-10 level was elevated of the two groups as compared with before treatment; moreover, the observation group exhibited superior indices as above to compare with the control group (P<0.05). (2) A total of 34 core targets of Liyin Decoction combined with Fengsui Decoction for the treatment of chronic pharyngitis were obtained, including IL-6, IL-10, and TNF, etc. The results of pathway enrichment analysis revealed that the intersection targets were mainly involved in signaling pathways of mitogen activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), TNF, etc. The results of functional enrichment analysis interpreted that the core targets participated in biological processes with respect to signal transduction, negative regulation of cell apoptosis process, reaction to medicines, etc., and were enriched in cellular compositions in terms of nucleus, cytoplasmic solute, nucleoplasm, etc., and were involved in molecular functions of protein binding, enzyme binding, transcription factor binding, etc. ConclusionLiyin Decoction combined with Fengsui Decoction for the treatment of chronic pharyngitis in spleen and stomach deficiency with cold manifestation exerts a favorable clinical effect, which can effectively ameliorate patients′ clinical symptoms, decrease serum inflammatory factors IL-6 and TNF-α levels, and increase serum IL-10 level. Its potential mechanism may be that multiple active pharmaceutical components can participate in the regulation of PI3K/AKT, TNF, MAPK and other inflammation-related signaling pathways, thereby inhibiting inflammations by acting on the core targets such as IL-6, TNF-α, IL-10.