Objective To observe the effect of hydroxychloroquine on lymphocyte distribution in the peripheral immune organs ( spleen) of systemic lupus erythematosus mice (TC mice). Methods Thirty-week-old femaleTC mice were randomly assigned to two groups: the experimental group was treated with hydroxychloroquine [10 mg / (kg·d)] and the control group was treated with normal saline [10 mg / ( kg·d)] for 5 weeks. Enzyme-linked immunosorbent assay was used to detect the titer of anti-dsDNA antibody in the peripheral blood of mice, Hematoxylin-eosin staining was used to detect histopathological changes in kidneys, and flow cytometry was used to detect the proportion of lymphocytes in the spleen of mice. Results The histopathological score of kidneys in the experimental group was significantly lower than that in the control group ( P< 0. 05). The proportions of splenic B lymphocytes and germinal center B lymphocytes in the experimental group were significantly lower than that in the control group (P< 0. 05). The proportion of splenic regulatory Tlymphocyte (Treg) in the experimental group was significantly higher than that in the control group (P< 0. 05). There were no significant difference in the levels of anti-dsDNA antibody and the T helper cell 17 ( Th17) lymphocyte proportions between groups (P > 0. 05 ). Conclusions Hydroxychloroquine has a regulatory effect on the immune response of lymphocytes in peripheral immune organs of lupus mice and alleviated the pathological damage in kidney tissues of TCmice.