Objective:To investigate the protective effect and mechanism of silymarin on bronchiolitis caused by respiratory syncytial virus (RSV) in mice.Methods:A mouse model of bronchiolitis was established by intranasal instillation of RSV. After successful modeling, the mice were randomly divided into a model group, a positive control group (ribavirin, 10 mg/kg), a low-dose silymarin group (25 mg/kg), a medium-dose silymarin group (50 mg/kg), and a high-dose silymarin group (100 mg/kg). In addition, a control group was established, with 12 mice in each group. The pulmonary index and RSV virus load were determined in each group of mice. Hematoxylin-eosin (HE) staining was used to observe the pathological changes in the lungs. The levels of interleukin-4 (IL-4), interferon-γ (IFN-γ), transforming growth factor-β (TGF-β), IL-17, and IL-10 in bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect the proportion of helper T cells 17 (Th17) and regulatory T cells (Treg) in peripheral blood. Western blot was used to detect the expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor κB subunit p65 (NF-κB p65), and phosphorylated nuclear protein p-NF-κB p65 in lung tissue.Results:Compared with the model group, the pulmonary injury and inflammatory response were significantly improved in the medium-and high-dose silymarin groups. The pulmonary indexes were (1.27±0.17)% and (0.94±0.10)%, respectively, and the RSV virus loads were (2.65±0.19) and (2.13±0.14), respectively, which were significantly lower than those in the model group (all P<0.05). The proportion of Th17 cells in peripheral blood was (4.47±0.19)% and (3.52±0.13)%, respectively, which was significantly lower than that in the model group (all P<0.05), while the proportion of Treg cells in peripheral blood was (0.88±0.08)% and (1.33±0.12)%, respectively, which was significantly higher than that in the model group (all P<0.05). The expression levels of IL-4 and IL-17 in BALF and the protein expression levels of TLR4/NF-κB signaling pathway related proteins in lung tissue were significantly lower than those in the model group (all P<0.05), while the expression levels of IFN-γ, TGF-β, and IL-10 in BALF were significantly higher than those in the model group (all P<0.05). Conclusions:Silymarin can regulate immune function and inhibit inflammatory response, thereby improving airway inflammation in bronchiolitis mice. The mechanism may be related to inhibit activation of TLR4/NF-κB signaling pathway.