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Objectives This study is aimed at identifying critical therapeutic targets of Astragalus membranaceus (Huangqi (HQ)) and investigating the effects and mechanisms of HQ treating uveitis. The potential drug targets of HQ and main active ingredients were obtained from the traditional Chinese medicine (TCM) systems pharmacology database and analysis platform (TCMSP, http://tcmspnw.com ). Materials and Methods Cytoscape software was used to identify the disease targets of uveitis. Drug targets and disease targets were compared, and intersected hubs were applied for the active ingredient-target network and protein-protein-interaction (PPI) network construction. Signaling pathway enrichment annotation was performed to identify possible signaling involved in uveitis treatment. An endotoxin-induced uveitis (EIU) model was established, and the therapeutic effects of total flavonoids of Astragalus (TFA) on uveitis were investigated by examining the improvement of eye symptoms, histopathological alterations, and the levels of cytokines. Results Based on network pharmacological analysis, HQ could modulate the initiation and progression of uveitis by reducing the production of cytokines and regulating cell apoptosis via the NOD-like receptor (NLR), apoptosis, and toll-like receptor (TLR) signaling pathways. Based on animal experiments, high-dose TFA could reduce rat’s iris congestion, reduce anterior chamber exudation and pus, restore pupil size, and decrease the release of inflammatory factors IFN-γ and IL-10. Network pharmacological and experimental analyses revealed that TFA regulates the release of inflammatory factors through the NLR and TLR signaling pathways, thus regulating the immune system of EIU rats and ultimately relieving inflammation responses in uveitis rats.