Abstract: To enhance the aquaculture efficiency and production output, farming practices have shifted from traditional single-mode pond systems to more intensive, higher density modes. With the increase in density, challenges such as frequent fish diseases have emerged, underscoring the importance of understanding immune mechanisms in aquatic animals. Neutrophils and macrophages serve as primary immune effectors, mediating innate immune response and bridging innate immune and adaptive immunity to combat pathogen invasion through phagocytosis, inflammation regulation, and antigen presentation. This review focuses on the regulatory mechanisms of granulocyte and macrophage development, updating progress on their roles in immune responses and the potential mechanisms. By synthesizing current knowledge of their differentiation and functions in fish immunity, this overview highlights their critical roles in host defense, and unscrambles the underlying genetic regulatory effects, including important economic trait genes and important breeding value genes. This will provide a theoretical basis for enhancing disease resistance in aquatic animal research, promoting the transformation of green and efficient aquaculture.