Ferret IL-22 (Interleukin-22) is a member of the IL-10 cytokine family that plays a key role in mucosal immunity and epithelial barrier protection in ferrets (Mustela putorius furo). IL-22 is produced primarily by activated CD4⁺ T cells, including Th17- and Th22-like populations, as well as by innate lymphoid cells (ILC3s) in response to microbial infection and inflammatory stimulation. It signals through the IL-22 receptor complex (IL-22R1 and IL-10R2), which is expressed mainly on epithelial and stromal cells, activating downstream JAK/STAT pathways—particularly STAT3—to induce antimicrobial peptide production, enhance chemokine expression, promote epithelial cell proliferation, and support tissue repair. In healthy ferrets, basal IL-22 expression is generally low but increases during bacterial, viral, and fungal infections, especially at mucosal surfaces of the respiratory and gastrointestinal tracts. In biomedical research, ferret IL-22 is particularly relevant in respiratory disease models such as influenza and SARS-CoV-2, where it contributes to epithelial defense and tissue regeneration while influencing inflammatory responses. Characterization of IL-22 in ferrets provides insight into mucosal immune regulation, host–pathogen interactions, and the balance between protective immunity and immunopathology in a widely used model of human respiratory infection.