Abstract: OBJECTIVE To investigate protective effects of total flavonoids from Mosla scabra(MSF) on bleomycin- induced pulmonary fibrosis of rats, and explore its preliminary mechanism. METHODS Sixty SD rats were divided into six groups randomly: normal group, model group, positive control group, MSF high-dose, middle-dose and low-dose treatment group. Pulmonary fibrosis in rats was induced by intratracheal instillation of belomycin (5 mg·kg^-1). After challenge of 14 d, the two treatment groups were given MSF at the doses of 40, 80 and 160 mg·kg^-1 respectively, while positive control group was treated with prednisone acetate (2 mg·kg^-1). Normal group and model group were treated with saline once a day for 28 d. The activities of SOD and GSH, the levels of IL-4, TNF-α, TGF-β1 and HA in serum were detected after molding 42 d. The histological examination was performed with Masson stain. The expression of α-SMA was detected by immunohistochemistry analysis while the expression of NF-κB, TNF-α, TGF-β1, Smad2/3 and pSmad2/3 proteins was detected by Western-blotting analysis.RESULTS Compared with the model group, the activities of SOD and GSH were increased significantly whereas levels of IL-4, TNF-α, TGF-β1 and HA in serum were decreased significantly after MSF treatment (P<0.01). The expression of a-SMA was down-regulated. The degree of fibrosis was reduced. The protein expressions of NF-κB, TNF-α, TGF-β1, Smad2/3 and pSmad2/3 were also significantly decreased (P<0.01). CONCLUSION MSF can ameliorate pulmonary fibrosis through inhibition of NF-κB and TGF-β1 signaling.