Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by the loss of tolerance to self-antigen. Because it is currently not known if regulatory T (Treg) cells are involved in the pathogenesis, we determined the frequency of CD4+CD25+ T cells and assayed the related gene expression levels in CD4+CD25+ T cells isolated from both lupus mice (NZB/NZW F1) and normal control mice (DBA2/NZW F1). The results showed that the frequency of CD4+CD25+ T cells in lupus mice was lower than that of normal mice. Except for the high expression level of interleukin (IL)-10 mRNA, CD4+CD25+ T cells from lupus mice expressed normal forkhead box P3 (Foxp3) and transforming growth factor (TGF)-β mRNA, and exerted suppressive functions. Furthermore, we depleted CD25+ Treg cells of non-autoimmune mice with anti-CD25 antibody and broke their tolerance with apoptotic cell-pulsed dendritic cells for the follow-up of autoantibody levels. The mice in the CD25+ cell-depleted group had higher titres of anti-double-strand/single-strand DNA antibodies than those of the isotype control antibody-treated group. These findings indicated that CD4+CD25+ T cells might be involved in the regulatory mechanism of autoantibody production.