Rat 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 containing the shared gp130 subunit to activate JAK/STAT and MAPK pathways. In rats (Rattus norvegicus), IL-6 is produced by macrophages, monocytes, endothelial cells, adipocytes, and other cell types in response to infection, tissue injury, metabolic stress, and immune stimulation, where it regulates acute-phase protein production, fever, leukocyte recruitment, and B- and T-cell differentiation. Rat IL-6 plays a critical role in widely used experimental models of sepsis, arthritis, neuropathic pain, cardiovascular disease, stroke, metabolic syndrome, and cancer, with elevated IL-6 levels correlating with inflammation severity and tissue damage. IL-6 is also a key mediator in models of neuroinflammation and traumatic brain injury, supporting investigation into cytokine-driven central nervous system pathology. As both a biomarker and therapeutic target, rat IL-6 is extensively utilized in preclinical pharmacology, toxicology, and immunology research to evaluate anti-inflammatory agents, biologics targeting the IL-6/IL-6R pathway, and novel immunomodulatory strategies, reinforcing its importance in translational biomedical studies.