Myeloid-derived suppressor cells with immunosuppressive functions have been described to be associated with one of the mechanisms by which malignant tumors escape immune surveillance. However, little is known about the role of myeloid-derived suppressor cells in autoimmunity. In the current study, when we attempted to characterize the peritoneal cells in pristane-induced lupus model, as reported previously, we observed that there were markedly increased CD11bl(+)y6C(hi) monocytes. Surprisingly, this type of monocytes was almost phenotypically identical to the reported monocytic myeloid-derived suppressor cells. Further analysis on how these CD11b(+)Ly6Chi(+) cells affected T cell response showed that they strongly suppressed T cell proliferation in vitro in a manner dependent on cell-cell contact, NO, and PGE2. In addition, we found that CD11bl(+)y6C(hi) monocytes inhibited Thl differentiation but enhanced development of forkhead box p3(+)CD4(+) regulatory T cells. Consistent with the in vitro experimental results, the in vivo adoptive cell transfer study showed that infusion of pristanetreated syngeneic CD11b(+)Ly6C(hi) monocytes significantly suppressed the production of anti -keyhole limpet hemocyanin antibodies induced by keyhole limpet hemocyanin immunization. In addition, we found that CD11b(+)Ly6C(hi) monocytes were also increased significantly in spleen and peripheral blood and showed immunosuppressive characteristics similar to their peritoneal counterparts. Our findings indicate that CD11b(+)Ly6C(hi) monocytes in a pristane-induced lupus mouse model are monocytic myeloid-derived suppressor cells instead of inflammatory monocytes, as demonstrated previously. To our knowledge, this is the first to describe myeloid-derived suppressor cells in a pristane-induced lupus mouse model, which may lead to a better understanding of the role of CD11b*Ly6Ch1 monocytes in this specific pristane-induced lupus model.