〔Abstract〕 To investigate the effects of astragalus mongholicus extract ( AME) on lung injury and the myeloid differentiation factor 88 ( MyD88) /Toll-like receptor 4 ( TLR4 ) /nuclear factor kappa B ( NF-κB) p65 pathway in rheumatoid arthritis induced interstitial lung disease (RA-ILD) rats . Methods SD rats were randomly divided into a control group , RA-ILD group , low-dose AME group (5 g/L) , high-dose AME group (10 g/L) , and high-dose AME + lipopolysaccharide (LPS) group ( 10 g/L AME + 1 mg/L TLR4 activator LPS) . Except for the control group , rats in all other groups were injected with bovine type Ⅱ collagen , Freund ’s complete adjuvant , and bleomycin to establish the RA-ILD model . The arthritis index and lung tissue wet-dry weight ratio of rats were tested . ELISA was applied to detect the levels of inflammatory factors interleukin (IL)-1β, IL-6 and tumor necrosis factor-α( TNF-α) in bronchoalveolar lavage fluid . Hematoxylin eosin staining was used to observe pathological changes of rat knee joint tissue and lung tissue . Western blot was applied to detect the expression of autophagy fac- tors Beclin 1 , microtubule-associated protein 1A/1B - light chain 3 (LC3) Ⅱ/ Ⅰ , and MyD88/TLR4/NF-κB p65 pathway related proteins in lung tissue . Results Compared with control group , knee joint tissue and lung tissue of rats in RA-ILD group were damaged , the arthritis index , lung tissue wet-dry weight ratio , levels of IL-1β, IL-6 , and TNF-α, the expression levels of MyD88 and TLR4 proteins , and p-NF-κB p65/NF-κB p65 ratio increased (P < 0. 01) , the expression of Beclin 1 and LC3 Ⅱ/ Ⅰ proteins decreased (P < 0. 01) . Compared with RA-ILD group , the low-dose and high-dose AME groups showed reduced tissue damage in rats , the arthritis index , lung tis- sue wet-dry weight ratio , levels of IL-1β, IL-6 , and TNF-α, the expression levels of MyD88 and TLR4 proteins , and p-NF-κB p65/NF-κB p65 ratio showed a dose-dependent decrease (P < 0. 05 or P < 0. 01), the expression of Beclin 1 and LC3 Ⅱ/ Ⅰ proteins showed a dose-dependent increase (P < 0. 05 or P < 0. 01) . Compared with high- dose AME group , the tissue damage of rats in the high-dose AME + LPS group was worsened , the arthritis index , lung tissue wet-dry weight ratio , levels of IL-1β, IL-6 , and TNF-α, the expression levels of MyD88 and TLR4 pro- teins , and p-NF-κB p65/NF-κB p65 ratio were higher (P < 0. 01), the expression of Beclin 1 and LC3 Ⅱ/ Ⅰ pro- teins was lower ( P < 0. 01) . Conclusion AME inhibits the MyD88/TLR4/NF-κB p65 pathway and alleviates lung injury in RA-ILD rats .