Objective: To investigate the effects of microRNA-146b (miR-146b) on the proliferation, secretion of inflammatory factors, and cell cycle of mesangial cells in mice with lupus nephritis and its potential mechanism. Methods: The targeting relationship between miR-146b and tumor necrosis factor receptor-associated factor 6 (TRAF6) was verified by dual luciferase reporter gene assay. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used to detect TRAF6 expression. The mesangial cells were divided into a miR-control group (negative control transfected with miR-146b mimic), a miR-146b mimic group (transfected with miR-146b mimic), a miR-146b mimic + NC group (co-transfected with miR-146b mimics and empty plasmid PCDNA-NC) and a miR-146b mimic + TRAF6 group (co-transfected with miR-146b mimics and TRAF6 overexpression plasmid). Cell counting kit 8 (CCK-8) and immunofluorescent staining were used to detect cell proliferation. The levels of inflammatory cytokines in supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Cell cycle was analyzed by flow cytometry. Results: MiR-146b targeted and negatively regulated the expression of TRAF6. Compared with miR-control group, the proliferation ability of cells in miR-146b mimic group was significantly decreased, the levels of inflammatory factors interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in cell supernatant were decreased, and the cells were arrested in G₀/G₁ phase. Overexpression of TRAF6 significantly reversed the inhibitory effect of miR-146b on the proliferation and secretory of inflammatory factors in mesangial cells, reduced the proportion of G₀/G₁ phase cells, and promoted the cells to enter into S phase. Conclusion: MiR-146b may alleviate the inflammatory damage of mesangial cells in lupus nephritis by targeting TRAF6.