〔Abstract〕 To establish a mouse model of lung injury induced by self-antigens and explore its pathological mechanisms to provide a reliable animal model for studying the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Method The mice were injected intradermal with antigenemulsion made of complete Freund's adjuvant (CFA) and lung tissue protein, and the emulsion prepared with incomplete Freund's adjuvant (IFA) was used to enhance immunity. HE staining was used to observe the histopathological changes in the mice. Masson staining was used to detect pulmonary fibrosis. The mRNA levels of rheumatoid factor (RF), Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) were detected by qPCR. The levels of ACPA, IgG1, IgG2a and IgG3 antibodies were detected by ELISA. The changes of inflammatory cells and α-smooth muscle actin (α-SMA)expression in lung tissue were detected by immunofluorescence staining. The protein expression levels of Collagen I and α-SMA were detected by Western blot. The changes of immune cells were detected by flow cytometry. Results HE staining showed that inflammatory cell infiltration increased and tissue structure changed significantly in lung tissue after the model was established by self-lung tissue antigen. Masson staining showed increased collagen deposition in lung tissue of model mice. qPCR tests revealed elevated mRNA levels of RF, KL-6 and SP-D.. ELISA tests revealed elevated levels of ACPA, IgG1 and IgG3 antibodies. Immunofluorescence results showed that monocytes and T cells increased, and α-SMA expression increased in the model group. Western blot results showed increased protein expressions of Collagen I and α-SMA. The flow cytometry results showed an increase in T cells and monocytes in the lung tissue. Conclusion The mouse model of lung injury induced by self-antigens is successfully established, and T cells and monocytes may be involved in the occurrence and progression of the disease.