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Microglia are resident immune cells in the central nervous system(CNS), it play an important role in both physiological and pathological conditions of the CNS, and can be activated by a variety of physicochemical factors to produce pro-inflammatory phenotype (M1 type) and anti-inflammatory phenotype (M2 type). Milk fat globule epidermal growth factor 8(MFG-E8) is closely related to the biological function of microglia, which can regulate microglia neuroprotective effects such as promoting phagocytosis, anti-inflammatory, and inhibiting oxidative stress in CNS related diseases. It also regulates microglia pro-tumor effect, which in turn affects the outcome of the disease. This article reviews the role of targeting MFG-E8 in regulating the function of microglia, and provides a basis for finding therapeutic targets for CNS related diseases in the future. [ABSTRACT FROM AUTHOR]