Equine Interleukin-6 (IL-6) is a multifunctional pro-inflammatory cytokine and a central member of the IL-6 cytokine family—including IL-6, IL-11, IL-27, IL-31, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), and cardiotrophin-like cytokine factor 1 (CLCF1)—which signal through receptor complexes utilizing the shared gp130 subunit to activate JAK/STAT and MAPK pathways. In horses (Equus caballus), IL-6 plays a critical role in regulating acute-phase protein production (including serum amyloid A and fibrinogen), leukocyte activation, B- and T-cell differentiation, and systemic inflammatory responses during infection, tissue injury, and exercise-induced stress. Elevated IL-6 levels are associated with common and economically significant equine conditions such as colitis, endotoxemia, equine influenza, strangles (Streptococcus equi infection), osteoarthritis, laminitis, and systemic inflammatory response syndrome (SIRS), where it contributes to fever, vascular changes, and disease severity. As a sensitive biomarker of inflammation, equine IL-6 is valuable for early disease detection, monitoring treatment response, and assessing post-exercise inflammatory status in performance horses. In veterinary and translational research, characterization of equine IL-6 and related cytokine family members supports studies of musculoskeletal inflammation, respiratory disease, sepsis, and immune regulation, enhancing comparative immunology efforts and the development of targeted immunomodulatory strategies to improve equine health and athletic performance.