Ferret Interleukin-1 Receptor Antagonist (IL-1Ra) is an anti-inflammatory cytokine produced by monocytes, macrophages, neutrophils, and other immune cells in ferrets (Mustela putorius furo) that serves as a natural regulator of IL-1–mediated inflammatory responses. IL-1Ra competitively binds to the IL-1 receptor type 1 (IL-1R1) without triggering downstream signaling, thereby blocking the pro-inflammatory effects of IL-1α and IL-1β and limiting activation of NF-κB and MAPK pathways that drive fever, leukocyte recruitment, and amplification of inflammation. In ferret health and research, IL-1Ra is particularly relevant in respiratory viral infection models such as influenza virus and SARS-CoV-2, where regulation of IL-1β–driven lung inflammation is critical for balancing viral clearance with prevention of excessive pulmonary pathology. The IL-1/IL-1Ra balance influences cytokine cascades associated with severe respiratory disease and potential cytokine storm–like responses. Because ferrets are widely used as translational models for human respiratory infections and antiviral therapeutic testing, characterization of IL-1Ra supports studies of inflammasome regulation, inflammatory resolution, and evaluation of anti-inflammatory or immunomodulatory interventions. As both a biomarker and functional mediator of immune regulation, ferret IL-1Ra plays an important role in understanding and modulating inflammatory responses in respiratory disease research.