Macrophages play vital roles in iron metabolism and are also modulated by iron. Macrophages are crucial to the recycling of iron and systemic iron homeostasis, and the functional heterogeneity of macrophages contributes to the different effects on iron metabolism. Conversely, iron can affect the development, function, and polarization of macrophages. Macrophages can initiate ferroptosis through a series of signaling pathways when overloaded with intracellular iron. Macrophages ferroptosis can aggravate local inflammatory reactions and promote the progression of various diseases such as metabolism, infection, and inflammation, so inhibiting macrophages ferroptosis may be an important therapeutic target. In addition, inhibiting M1-like macrophages ferroptosis and promoting M2-like macrophages ferroptosis are important in inhibiting the progression of malignant tumors.