Abstract: This study aimed to investigate the protective effect of total alkaloids(TA)and one of the active components, neotuberostemonine, of Stemona tuberosa on bleomycin-induced pulmonary fibrosis in mice and to explore the mechanism by fibroblasts model. The bleomycin-induced mice were orally administered with TA(60 mg/kg)and neotuberostemonine(10, 20 mg/kg), with prednisone(6. 67 mg/kg)as a positive control. The anti-fibrotic effects were assessed by hydroxyproline content, TGF-β1 level, inflammatory score, collagen deposition and the expression of α-SMA in the lung tissues. The results revealed that TA and neotuberostemonine could significantly ameliorate the inflammation and injury, and attenuate the hydroxyproline content and collagen deposition. Moreover, neotuberostemonine treatment markedly down-regulated the α-SMA level and TGF-β1 content in bleomycin-injured mice lungs. The in vitro experiments showed that neotuberostemonine inhibited the expression of α-SMA induced by TGF-β1 in a dose-dependent manner, indicating that suppression on differentiation of fibroblasts to myofibroblasts may be one of the mechanisms for neotuberostemonine against pulmonary fibrosis.