Chicken Interleukin-8 (IL-8), also referred to as CXCLi2 (and closely related to CXCLi1 in avian species), is a key pro-inflammatory chemokine that regulates heterophil chemotaxis and activation in chickens (Gallus gallus). Functionally analogous to mammalian IL-8, chicken IL-8 is produced by macrophages, epithelial cells, and other immune cells in response to bacterial, viral, and parasitic infections, and signals through CXCR1- and CXCR2-like receptors to promote recruitment of heterophils—the avian equivalent of neutrophils—to sites of infection or tissue damage. IL-8 is rapidly upregulated during economically significant diseases such as avian influenza, Newcastle disease, infectious bronchitis, Salmonella infection, Eimeria (coccidiosis), and necrotic enteritis, where it plays a central role in early innate immune defense but can also contribute to inflammatory tissue pathology if dysregulated. Elevated IL-8 expression in respiratory and intestinal tissues serves as a valuable biomarker of mucosal immune activation and disease severity in poultry. In research settings, chickens are established animal models for avian influenza virus pathogenesis, Salmonella enterica colonization and foodborne transmission studies, Eimeria-induced intestinal inflammation models, Campylobacter infection, and vaccine development platforms, as well as developmental immunology research due to the accessibility of the avian embryo. Characterization of IL-8 in these specific models enhances understanding of chemokine-driven heterophil recruitment, mucosal immune defense, inflammatory regulation, and vaccine-induced protection, providing comparative insight into neutrophil-mediated immunity relevant to both veterinary medicine and human infectious disease research.