Abstract: Objective To clarify the mechanism by which interleukin-22 (IL-22) promotes the proliferation of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Methods FLS were isolated from the synovial tissues of patients with RA and identified by immunohistochemistry for vimentin/CD68. The cells were subcultured and incubated with different concentrations of IL-22 for 24, 48, or 72 h, and their proliferation was examined using MTT assay. After treatment of the cells with IL-22 and AG490, alone or in combination, the expressions of the total and phosphorylated proteins of STAT3, ERK1/2 and P38 were detected with Western blotting. Results IL-22 significantly increased the proliferation of FLS in a dose-dependent manner (P<0.05). The total protein of STAT3 in the cells showed no significant changes with extended time of IL-22 treatment (P=0.68), but the expression of phosphorylated STAT3 protein increased significantly (P<0.001). The total and phosphorylated proteins of ERK1/2 and P38 underwent no significant changes after IL-22 treatment (P>0.05). A combined treatment with 50 ng/mL IL-22 and 100 μmol/L AG490 resulted in a significant decrease in the proliferation of FLS as compared with IL-22 treatment alone (P<0.01). Conclusion IL-22 can dose-dependently promote the proliferation of FLS from patients with RA by inducing phosphorylation of STAT3 protein but not through ERK1/2 or P38 signal pathway.