Macrophages are the core of the pathophysiology of rheumatoid arthritis (RA). They participate in specific and non-specific immunological responses, have phagocytosis, chemotaxis and immune regulatory functions, and are involved in the onset and progression of RA. In recent years, research on the pathophysiology of RA has focused on the polarization and functions of classically activated M1 and selectively activated M2 macrophage subtypes. M1 macrophages release different proinflammatory cytokines, thus driving the chronic proinflammatory, tissue destruction and pain response in RA. M2 macrophages play an anti-inflammatory role. Because of the important role of monocyte-macrophage in RA, drug research targeting monocyte-macrophage can bring us more hope for treatment of RA. This study reviewed the characteristics, plasticity, molecular activation mechanism and relationship of RA with mononuclear macrophages, as well as the transformative potential of macrophages in developing new therapeutic drugs for clinical practice.