A large phagocytic cell (see phagocyte) that can ingest pathogenic microorganisms (e.g. bacteria, protozoa) or cell debris and forms part of the body’s immune system. Macrophages develop from precursor cells (promonocytes) in bone marrow, become wandering monocytes in the bloodstream, and then settle as mature macrophages in various tissues, including lymph nodes, connective tissues (as histiocytes), lungs (alveolar macrophages), lining of liver sinusoids (as Kupffer cells), skin (as Langerhans cells), and nervous tissues (microglia). The sinusoids of the spleen are lined with macrophages that remove worn-out red cells and platelets from the blood and destroy them. Collectively the macrophages make up the mononuclear phagocyte system.

Macrophages express surface receptors (see toll-like receptor) that recognize and bind to common surface components of bacteria, viruses, fungi, and other pathogens. Such binding activates the macrophage, causing it to engulf microbial pathogens and also to secrete various cytokines and chemokines, which attract leucocytes (e.g. neutrophils and monocytes to the infection site, initiate inflammation, trigger the acute-phase response, and activate natural killer cells. Macrophages also recognize and bind to microbial surfaces that have been coated with complement proteins (see complement receptor). Signals from T_H1 helper T cells play a crucial role in stimulating macrophages to destroy their ingested bacteria, by increasing the expression of inducible nitric oxide synthase (iNOS). Nitric oxide (NO), superoxide anion (O₂⁻), and hydrogen peroxide (H₂O₂) are all toxic effector molecules produced by macrophages to kill engulfed microorganisms. Activated macrophages can also act as antigen-presenting cells and activate T cells, as the first step to an adaptive immune response.