Interleukins (ILs) are potent secreted regulators of a wide range of cell types and cellular activities, particularly in the immune system. They are able to participate in intercellular communication in homeostasis and disease, thereby exerting immune functions. Macrophages serve as the innate immune cells of vertebrates and play a pivotal role in defending against and eliminating external pathogens. In mammals, the immune response mounted by macrophages is intricately linked to ILs. Given the fact that teleost fish have evolved an innate immune system that closely resembles those of mammals, particularly in terms of the functionality of macrophages, raises the intriguing possibility that the regulatory function of ILs in macrophage-mediated immunity might be evolutionarily conserved across both mammal and teleost fish lineages. Consequently, from the perspective of interleukin regulation of macrophages, this review outlines the relationship between ILs and macrophages in teleost fish, and elucidates the regulatory role of ILs of immune cell function in teleost fish, thereby contributing to our understanding of the key role of these cytokines in the prevention and control of aquaculture diseases.