Macrophages (/ˈmækroʊfeɪdʒ/; abbreviated Mφ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This self-protection method can be contrasted with that employed by Natural Killer cells. This process of engulfment and digestion is called phagocytosis; it acts to defend the host against infection and injury.

Macrophages are found in essentially all tissues, where they patrol for potential pathogens by amoeboid movement. They take various forms (with various names) throughout the body (e.g., histiocytes, Kupffer cells, alveolar macrophages, microglia, and others), but all are part of the mononuclear phagocyte system. Besides phagocytosis, they play a critical role in nonspecific defense (innate immunity) and also help initiate specific defense mechanisms (adaptive immunity) by recruiting other immune cells such as lymphocytes. For example, they are important as antigen presenters to T cells. In humans, dysfunctional macrophages cause severe diseases such as chronic granulomatous disease that result in frequent infections.

Beyond increasing inflammation and stimulating the immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines. Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages. This difference is reflected in their metabolism; M1 macrophages have the unique ability to metabolize arginine to the "killer" molecule nitric oxide, whereas M2 macrophages have the unique ability to metabolize arginine to the "repair" molecule ornithine. However, this dichotomy has been recently questioned as further complexity has been discovered. Macrophages are widely thought of as highly plastic and fluid cells, with a fluctuating phenotype.

Human macrophages are about 21 micrometres (0.00083 in) in diameter and are produced by the differentiation of monocytes in tissues. They can be identified using flow cytometry or immunohistochemical staining by their specific expression of proteins such as CD14, CD40, CD11b, CD64, F4/80 (mice)/EMR1 (human), lysozyme M, MAC-1/MAC-3 and CD68.

Macrophages were first discovered and named by Élie Metchnikoff, a Russian Empire zoologist, in 1884.

A majority of macrophages are stationed at strategic points where microbial invasion or accumulation of foreign particles is likely to occur. These cells together as a group are known as the mononuclear phagocyte system and were previously known as the reticuloendothelial system. Each type of macrophage, determined by its location, has a specific name:

Investigations concerning Kupffer cells are hampered because in humans, Kupffer cells are only accessible for immunohistochemical analysis from biopsies or autopsies. From rats and mice, they are difficult to isolate, and after purification, only approximately 5 million cells can be obtained from one mouse.

Macrophages can express paracrine functions within organs that are specific to the function of that organ. In the testis, for example, macrophages have been shown to be able to interact with Leydig cells by secreting 25-hydroxycholesterol, an oxysterol that can be converted to testosterone by neighbouring Leydig cells. Also, testicular macrophages may participate in creating an immune privileged environment in the testis, and in mediating infertility during inflammation of the testis.