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In vertebrates, primitive macrophages first develop in yolk sac hematopoiesis and differentiate into fetal macrophages. Monocytes are differentiated from hematopoietic stem cells in the late stage of fetal hematopoietic organs and bone marrow. Macrophages serve as an effector in metabolism and host defense. Depletion of macrophages severely reduced bilirubin production and host resistance to infection. Macrophage scavenger receptors are involved in host defense. Macrophage growth factors are critical for macrophage differentiation and function. In macrophage colony stimulating factor- deficient osteopetrotic mice, monocytes, tissue macrophages and osteoclasts are deficient. Granulocyte macrophage colony stimulating factor-deficient mice develop alveolar proteinosis due to impaired surfactant catabolism by alveolar macrophages. Accumulation of glucocerebroside in macrophages in lysosomes produces Gaucher cells. Macrophages incorporate chemically modified low-density lipoprotein (LDL) and transform into foam cells. Binding oxidized LDL to liver X receptor \u03b1 (LXR\u03b1) upregulates the expression of its target genes, which act as cholesterol removers from macrophages. Inflammatory signals downregulate the expression of LXR\u03b1 and enhance lipid accumulation. 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