Equine GM-CSF (Granulocyte–Macrophage Colony-Stimulating Factor, CSF2) is a hematopoietic cytokine belonging to the colony-stimulating factor family, which also includes G-CSF (CSF3) and M-CSF (CSF1) that regulate the development, proliferation, and activation of myeloid immune cells. In horses (Equus caballus), GM-CSF is produced by activated T lymphocytes, macrophages, endothelial cells, fibroblasts, and other stromal cells in response to infection, inflammatory cytokines, or immune stimulation. Equine GM-CSF binds to the GM-CSF receptor (CSF2R) expressed on hematopoietic progenitor cells and mature myeloid cells, activating intracellular signaling pathways such as JAK/STAT, MAPK/ERK, and PI3K–AKT, which promote the proliferation and differentiation of granulocytes, macrophages, and dendritic cells, as well as enhance their functional activity in innate and adaptive immune responses. In equine health, GM-CSF contributes to immune defense and inflammatory regulation, particularly through activation of macrophages and neutrophils during infection or tissue injury. Horses are also used as animal models for respiratory inflammatory diseases, and GM-CSF–regulated myeloid responses have been studied in equine models of recurrent airway obstruction (heaves), where activation of macrophages and granulocytes contributes to airway inflammation, providing insights relevant to both equine respiratory disease and human asthma research.