BACKGROUND: Rheumatoid arthritis (RA) is a chronic, invasive autoimmune disease characterized by symmetrical polyarthritis involving synovial inflammation. Epidemiological studies indicate that the incidence of RA continues to rise, yet the pathogenesis of this disease remains not fully understood. A significant infiltration of macrophages is observed in the synovium of RA patients. It can be inferred that macrophages likely play a crucial role in the onset and progression of RA. SUMMARY: This review aims to summarize the research progress on the mechanisms by which macrophages and their associated structures contribute to RA, as well as potential therapeutic approaches, aiming to provide new insights into the study of RA pathogenesis and its clinical treatment. KEY MESSAGES: During the course of RA, besides the inherent roles of macrophages, these cells respond to microenvironmental changes such as pathogen invasion or tissue damage by undergoing polarization, pyroptosis, or forming macrophage extracellular traps (METs), all of which influence inflammatory responses and immune homeostasis, thereby mediating the occurrence and development of RA. Additionally, macrophages secrete exosomes, which participate in intercellular communication and signal transduction processes, thus contributing to the progression of RA. Therefore, it is critical to elucidate how macrophages and their related structures function in RA. BACKGROUND: Rheumatoid arthritis (RA) is a chronic, invasive autoimmune disease characterized by symmetrical polyarthritis involving synovial inflammation. Epidemiological studies indicate that the incidence of RA continues to rise, yet the pathogenesis of this disease remains not fully understood. A significant infiltration of macrophages is observed in the synovium of RA patients. It can be inferred that macrophages likely play a crucial role in the onset and progression of RA. SUMMARY: This review aims to summarize the research progress on the mechanisms by which macrophages and their associated structures contribute to RA, as well as potential therapeutic approaches, aiming to provide new insights into the study of RA pathogenesis and its clinical treatment. KEY MESSAGES: During the course of RA, besides the inherent roles of macrophages, these cells respond to microenvironmental changes such as pathogen invasion or tissue damage by undergoing polarization, pyroptosis, or forming macrophage extracellular traps (METs), all of which influence inflammatory responses and immune homeostasis, thereby mediating the occurrence and development of RA. Additionally, macrophages secrete exosomes, which participate in intercellular communication and signal transduction processes, thus contributing to the progression of RA. Therefore, it is critical to elucidate how macrophages and their related structures function in RA.