Objective To explore the effect and mechanism of silybin on improving pulmonary fibrosis and oxidative stress in mice. Methods A total of 120 mice were randomly divided into sham operation group, lung injury model group, dexamethasone group, low-dose, medium-dose and high-dose silybin groups (20 mice each). The models of pulmonary injury mice were induced by bleomycin. Mice in dexamethasone group, low-, medium- and high-dose silybin groups were given intragastric administration of dexamethasone (3 mg/kg) and silybin (120, 240, 480 mg/kg), while sham operation group and lung injury model group were given the same volume of normal saline for 28 d. The bronchoalveolar lavage fluid (BALF) and pulmonary tissues of each group were collected. The count of inflammatory cells in BALF was examined by microscopy. The pathological damage of pulmonary tissues was observed by HE staining. The pulmonary wet/dry weight ratio (W/D) was detected by wet-dry weighting method. The content of hydroxyproline (HYP) in pulmonary tissues, and levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β in BALF were detected by ELISA. The expressions of bone morphogenetic protein 9 (BMP9)/bone morphogenetic protein receptor 2(BMPR2)/SMAD signaling pathways-related proteins were detected by Western blotting. Results Compared with sham operation group, count of BALF inflammatory cells, scores of pulmonary injury and fibrosis, W/D, HYP, and MDA, TNF-α, IL-1β and IL-6 levels in BALF increased significantly, while SOD, GSH-Px activity, T-AOC levels in BALF, as well as the relative expression levels of BMP9, BMPR2 and p-SMAD1/5/9 in lung tissues decreased significantly in lung injury model group (P<0.05). Compared with lung injury model group, count of BALF inflammatory cells, scores of pulmonary injury and fibrosis, W/D, HYP, and MDA, TNF-α,IL-1β and IL-6 levels in BALF decreased significantly, while SOD, GSH-Px activity, T-AOC level in BALF, and BMP9, BMPR2 and p-SMAD1/5/9 expression levels in lung tissues increased significantly in high-dose silybin group and dexamethasone group(P<0.05). Conclusion The silybin may improve bleomycin-induced pulmonary fibrosis and oxidative stress in lung injury mice by mediating BMP9/SMAD signaling pathways, and thereby repairing pulmonary injury.