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Objective: The purpose of this study is to reveal the mechanism of action of Yi Qi Tong Qiao Pill (YQTQP) in the treatment of allergic rhinitis (AR), as well as establish a paradigm for the researches on traditional Chinese medicine (TCM) from systematic perspective. Methods: Based on the data collected from TCM-related and disease-related databases, target profiles of compounds in YQTQP were calculated through network-based algorithms and holistic targets of TQTQP was constructed. Network target analysis was performed to explore the potential mechanisms of YQTQP in the treatment of AR and the mechanisms were classified into different modules according to their biological functions. Besides, animal and clinical experiments were conducted to validate our findings inferred from Network target analysis. Results: Network target analysis showed that YQTQP targeted 12 main pathways or biological processes related to AR, represented by those related to IL-4, IFN-γ, TNF-α and IL-13. These results could be classified into 3 biological modules, including regulation of immune and inflammation, epithelial barrier disorder and cell adhesion. Finally, a series of experiments composed of animal and clinical experiments, proved our findings and confirmed that YQTQP could improve related symptoms of AR, like permeability of nasal mucosa epithelium. Conclusion: A combination of Network target analysis and the experimental validation indicated that YQTQP was effective in the treatment of AR and might provide a new insight on revealing the mechanism of TCM against diseases. Trial registration Name of the registry: Chinese Clinical Trial Registry: Trial registration number: ChiCTR-TRC-13,003,137: Date of registration: Registered 29 March 2013 - Retrospectively registered: URL of trial registry record: https://www.chictr.org.cn/showproj.html?proj=6422. [ABSTRACT FROM AUTHOR]