Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Although many drugs ? immunomodulatory and anti-fibrotic drugs ? have been tried for the treatment of IPF, they have not shown definite efficacy in preventing the progression of IPF. In the present study, we investigated the anti-fibrosis mechanism of SFN derivatives such as GSF-016 and GSF-018 on pulmonary fibrosis both in vivo BLM-induced model and in vitro TGF-?1-induced model. At first, in vivo studies, BLM was observed to induce pulmonary fibrosis in the lungs versus the controls, and SFN derivatives significantly attenuated. The expression levels of fibrosis-related proteins and mRNAs were significantly decreased in the BLM+GSF-016 group and BLM+GSF-018 group compared with the BLM group. Secondly, we further investigated the inhibitory mechanism of SFN derivatives on pulmonary fibrosis induced by TGF-?1 in diseased human lung fibroblast IPF cells. The results that GSF-016 or GSF-018 treatment attenuated TGF-?1-induced expression of fibrosis-related proteins and mRNAs in common with in vivo results. Furthermore, these compounds treatment significantly inhibited the migration of cell, invasion of cell and collagen gel contraction activity of fibrotic cells. These results that GSF-016 or GSF-018 treatment were founded to regulation of TGF-b1 signaling pathway mediators, such as smad, MAPK, Rho kinase and MRTF/SRF. In summary, our results demonstrated that GSF-016 or GSF-018 could alleviate experimental pulmonary fibrosis both in vivo and in vitro, suggesting that SFN derivatives has great potential for pulmonary fibrosis treatment.