〔Abstract〕 Absteact Objective To investigate the immunopathological changes of B lymphocyte activation in MRL/lpr lupus-like mice. Methods 20-week-old female MRL/lpr mice were sacrificed by cervical dislocation. The index of thymus and spleen of mice were calculated. The ratio of T lymphocyte subsets, total B cells and plasma cells in spleen lymphocyte suspension were analyzed with flow cytometry. Kidney and spleen pathology were observed with HE staining. The level of immune complex C3 expression in kidney and IL-21 mRNA in spleen were detected by immunofluorescence and q-PCR respectively. Serum IgG1, IgG2 a, ANA, anti-dsDNA, B lymphocyte stimulating factor(BLyS) and IL-10 levels were examinated by ELISA kits. The 20-week-age female BALB/c mice were used as control. Results Compared with the control group, the spleen and thymus index of MRL/lpr mice increased significantly, the proportion of TFH cells, Th17 cells, activated T cells and plasma cells increased while total B cells and immature T cells decreased obviously, and the differences were statistically significant. Furthermore, the C3 immune complex in glomerulus in kidney and the levels of serum IgG1, IgG2 a, anti-dsDNA, ANA, BLyS and IL-10 in MRL/lpr mice increased remarkably, displaying an interstitial nephritis. The spleen HE staining result of model mice displayed diffuse proliferation of white pulp, and the expression of IL-21 in spleen distinctly increased. The differences were statistically significant. Conclusion Similar with SLE, MRL/lpr mice display distinct interstitial nephritis which includes B lymphocyte hyperactivation, a mass of autoantibodies, immune complex deposition and high levels of BLyS, IL-10, IL-21.