Background:Yiqi TuominDecoction (YTD), which originated from the theory of lung deficiency and cold in Chinese medicine, is a common Chinese herbal formula used against allergic rhinitis (AR). In our otolaryngology department, this prescription has been used to treat so many AR patients with lung-deficiency-related colds for nearly 30 years. However, the mechanism of its ingredient–target is still unclear. Based on our early experiments and clinical case studies, in this paper, we explore the mechanism of YTD systematically against AR using bioinformatic methods of network pharmacology and molecular docking.Methods:The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen the active ingredients and targets of YTD. The AR-related targets were retrieved from OMIM, GeneCards, TTD, DisGeNET, DrugBank databases, and PharmGKB. The Venn database was used to screen the potential core targets. After that, the STRING database was used to construct the protein–protein interaction (PPI) of the core targets and then visualize it by Cytoscape. The Gene Ontology (GO)-enriched processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the core targets were analyzed by the KOBAS-I database and Sangerbox. Molecular docking was used to assess interactions between potential targets and active ingredients.Results:A total of 169 active ingredients and 238 targets of YTD were predicted. YTD shared 115 common targets with AR from the Venn database. The GO-enriched processes and KEGG pathways indicate that genes involved in inflammation and oxidative stress, accompanying the MAPK signaling pathway, Th17 cell differentiation, IL-17 signaling pathway, and Th1 and Th2 cell differentiation, may play a mediated effect in YTD. The docking results showed good binding ability between the active ingredients and the selected targets.Conclusions:Our study systematically indicated the underlying mechanism of YTD against AR from the perspective of bioinformatics. By studying the active ingredients of YTD, we obtained molecular mechanisms and established a reliable method and molecular theoretical basis for the sensible development of Chinese medicine in the treatment of AR.