〔Abstract〕 Objective To investigate the effect and mechanism of methyltransferase-like 3(METTL3) on the proliferation, migration, and secretion of inflammatory factors by synovial fibroblasts from rheumatoid arthritis(RA). Methods The expression of METTL3 in synovial tissue(SF) from 25 patients with rheumatoid arthritis and 25 patients with osteoarthritis was detected by RT-qPCR and immunohistochemistry, respectively. The concentration of RNA m6A was detected by ELISA. RA synovial fibroblasts were isolated and cultured, and divided into NC(normal control) group, hi-METTL3(overexpression of METTL3) group, si-METTL3(knock-down METTL3) group, and STM2457(METTL3 specific inhibitor) intervention group. Cell proliferation was detected by CCK-8 method. Apoptosis was detected by flow cytometry. And the concentrations of interleukin-6(IL-6), interleukin-17A(IL-17A), receptor activator of nuclear factor-kappa B ligand(RANKL), and osteoprotegerin(OPG) in the supernatant of cell culture were detected by ELISA. Results Compared with synovial tissue of osteoarthritis, the expression of mRNA m6A and METTL3 in synovial tissue of RA significantly increased(P<0.05). After overexpression of METTL3, the expression of m6A in synovial fibroblasts increased. The proliferation and migration abilities of SF in hi-METTL3 group were significantly improved, and their apoptosis did not change significantly. The secretion of cytokines IL-6 and RANKL of SF in hi-METTL3 group significantly increased, while the OPG significantly decreased(P<0.05). After interfering with METTL3 expression, the expression of m6A in synovial fibroblasts decreased. Cell proliferation and migration of SF in siMETTL3 group significantly decreased. The secretion of cytokines IL-6 and RANKL significantly decreased, and OPG significantly increased(P<0.05). After intervention with METTL3 inhibitor STM2457, the proliferation and migration of synovial fibroblasts were significantly reduced, and the secretion of cytokines IL-6 and RANKL significantly reduced, and OPG significantly increased(P<0.05). There was no significant difference in the expression of IL-17A among each group. Conclusion METTL3 may promote the proliferation and migration of RA synovial fibroblasts, enhance the expression of IL-6 and RANKL, and inhibit the expression of OPG through RNA m6A methylation modification.