Background and Purpose：Pulmonary fibrosis (PF) is the most common type of chronic lung disease, with a poor prognosis and a high mortality rate; however, treatment of PF is still a heavy burden. Astragaloside (AST), a major active component of Astragalus membranaceus, has demonstrated numerous pharmacological actions in a variety of diseases, including inflammation and tumors. It is worth noting that AST also plays an important role in the treatment of fibrotic diseases, but the mechanisms are still unknown. This study aims to further investigate the precise mechanisms of anti-fibrosis actin.Experimental Approach：To assess the anti-fibrosis effect of AST in PF mice, we determined the level of inflammation and collagen deposition in the lung tissue of PF mice. And we investigated whether the increased inflammation and collagen deposition shown in PF mice and human lung fibroblasts (HLF) cells are mediated by the upregulation of autophagy by inhibiting the Ras/Raf/MEK/ERK signaling pathway.Key Results: Our initial intriguing discovery was that AST has a significant therapeutic effect on reducing collagen deposition and anti-inflammatory effects in PF mice. This therapeutic effect of ATS could be attributed to autophagy activation. Additionally, siRNA-mediated autophagy deficiency exacerbates collagen deposition in HLF. Mechanistically, AST was demonstrated a functional dephosphorylation of MEK and ERK to inhibit the Ras/Raf/MEK/ERK signaling pathway, further notice autophagy was activated to varying degrees by agent depressors of Ras or MEK.Conclusion and Implications: our findings support the possibility that a therapeutic potential of AST for PF linking the de-repression mediated Ras/Raf/MEK/ERK signaling pathway via modulation of autophagy.