Swine Interleukin-1 Receptor Antagonist (IL-1Ra) is an anti-inflammatory cytokine produced by monocytes, macrophages, neutrophils, and other immune cells in pigs (Sus scrofa domesticus) that serves as a key endogenous regulator of IL-1–mediated inflammatory responses. IL-1Ra competitively binds to the IL-1 receptor type 1 (IL-1R1) without initiating intracellular 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, endothelial activation, and acute-phase responses. In swine health, IL-1Ra plays an important role in modulating inflammation associated with economically significant diseases such as porcine reproductive and respiratory syndrome (PRRS), swine influenza, African swine fever, bacterial pneumonia, enteric infections, and sepsis, where balancing IL-1 activity is critical to reducing tissue damage while maintaining pathogen clearance. The IL-1/IL-1Ra ratio can influence disease severity, lung pathology, and growth performance. As a biomarker of anti-inflammatory regulation, swine IL-1Ra is valuable in vaccine evaluation and immune modulation studies. In translational research, pigs serve as important large-animal models for human sepsis, trauma, and inflammatory disorders due to physiological similarities to humans, and characterization of swine IL-1Ra supports investigations into inflammasome regulation, cytokine network balance, and development of IL-1–targeted therapeutic strategies relevant to both veterinary and human medicine.