Forkhead Box P3 (Foxp3) is a lineage-specific transcription factor that controls the differentiation of CD4(+) regulatory T cells. The expression of Foxp3 in regulatory T cells is crucial for the upregulation of immunosuppressive effector molecules, whereby Foxp3 disruption leads to the breakdown of immune tolerance and the development of autoimmune disease. The present study reveals how CD11b(+) F4/80(+) macrophages also express Foxp3; it is not solely restricted to T cells in the immune system. The expression of Foxp3 in CD11b(+) F4/80(+) macrophages endows them with immunosuppressive ability. Foxp3(+) macrophages were subjected to global gene expression and proteomic analyses to reveal their unique profile, demonstrating how the mode by which Foxp3(+) macrophages exert their function involves the upregulation of immunoregulatory pathways. This finding indicates that Foxp3 is more widely expressed in the immune cells than previously thought.