Abstract: Objective:To investigate the effect of interleukin (IL)-35 subunits on lung and skin inflammation and pulmonary fibrosis in systemic sclerosis (SSc) mice.Methods:24 female BALB/c mice were randomly di-vided into four groups:normal control group, SSc model group, SSc+Epstein-Barr virus-induced gene 3 antibody(EBI3 mAb) group and SSc+IL-12Ap35 antibody (SSc+P35 mAb) group.Except for the normal control group, mice in the other groups were injected with bleomycin to establish the SSc model.After modeling, the SSc+EBI3 mAb group and SSc+P35 mAb group were injected with 100 μL of EBI3 mAb and P35 mAb by intraperitoneal injection, respectively.The skin and lung tissue inflammatory histological changes were observed by hematoxy-lin-eosin (HE)staining, the degree of pulmonary fibrosis was observed by Masson staining, α-smooth muscle ac-tin (α-SMA) expression in skin and lung tissue was detected by immunohistochemistry and the serum levels of IL-35, IL-6, and IL-10 were detected by enzyme linked immunosorbent assay (ELISA).Results:Compared with the control group, mice in the SSc model group showed an increase in skin thickness, pulmonary fi-brosis score, skin and lung tissue inflammation score, serum IL-35 level, and α-SMA expression in skin and lung tissue, as well as a decrease in serum IL-10 lev-el (all P< 0.05).Compared with the SSc model group, the skin thickness of mice in the SSc+EBI3 mAb group and SSc+P35 mAb group increased, serum IL-10 level and α-SMA expression in skin and lung tissue increased, and serum IL-35 level decreased (all P< 0.05).Compared with the SSc group, the mice in the SSc+P35 mAb group had a higher pulmonary fibrosis score(P< 0.05).Compared with the SSc+EBI3 mAb group, the serum IL-10 level in the SSc+P35 mAb group of mice increased(P< 0.05).Conclusion:IL-35 may inhibit skin and pulmo-nary fibrosis in the SSc mouse model through EBI3 and P35 subunits, but has no significant effect on inflamma-tion.The role of P35 subunits in pulmonary fibrosis is more obvious.