[Abstract] Objective: The effects of S100A9 knockout on mice with lupus nephritis induced by pristane were explored, for the purposes to clarify the specific roles of S100A9 on lupus nephritis. Methods: Ten female wild-type (WT) C57BL/6 mice and 10 S100A9-/- C57BL/6 mice (8-week-old) were studied. Five WT B6 mice and 5 S100A9-/- mice were intraperitoneally injected with 0.5 mL pristane, respectively serving as an experimental group. In addition, 5 WT B6 mice and 5 S100A9-/- mice were intraperitoneally injected with 0.5 mL normal saline, serving as control group. The mice were sacrificed at 6 months after injection. Autoantibody (anti-ds-DNA antibody) was measured by ELISA. Serum creatinine, serum urea nitrogen and urine protein were detected. Renal tissue was collected for HE staining to evaluate renal pathology. Results: There is no significant difference between WT and S100A9-/-B6 mice. Compared with control B6 mice, pristane treated B6 mice showed increased spleen weight, length of spleen, serum creatinine, urea nitrogen, proteinuria, anti-ds DNA antibody, IgG. Pristane treated B6 mice also showed increased glomerular volume, edema of renal tubule epithelium, lumen stenosis. Similarly, pristane-treated S100A9-/-B6 mice showed increased spleen weight, length of spleen, serum creatinine, urea nitrogen, proteinuria, anti-ds DNA antibody than those of control S100A9-/-B6 mice. And pristane-treated S100A9-/-B6 mice displayed typical characteristic of lupus nephritis. However, compared with pristane-treated WT B6 mice, the above symptoms of lupus nephritis and indexes of serum and urine in pristane-treated S100A9-/-B6 mice were mild. Conclusion: Pristane can induced SLE in B6 mice and S100A9-/- mice. However, but the degree of lesions in mice with S100A9 gene knockout is mild, suggesting that this gene is beneficial to the pathogenesis of lupus mice.