Chicken IL-21 (Interleukin-21) is a cytokine of the common γ chain (γc) family that plays an important role in regulating adaptive immune responses in chickens (Gallus gallus). IL-21 is produced primarily by activated CD4⁺ T cells, particularly T follicular helper (Tfh)-like and Th17-like cells, following antigen stimulation. It signals through the IL-21 receptor (IL-21R) in association with the common γ chain, activating downstream JAK/STAT pathways—especially STAT3—to regulate gene expression in target immune cells. IL-21 promotes B cell proliferation, differentiation, and antibody production, supports cytotoxic T lymphocyte responses, and enhances natural killer (NK)-like cell activity, thereby contributing to both humoral and cell-mediated immunity. In healthy chickens, basal IL-21 expression is generally low but increases during infection, vaccination, and immune activation. Elevated or dysregulated IL-21 responses have been associated with viral infections such as Marek’s disease virus (MDV), infectious bursal disease virus (IBDV), avian influenza virus, and Newcastle disease virus, as well as parasitic infections including Eimeria spp. (coccidiosis). Chickens serve as important animal models for viral oncogenesis (MDV as a model for herpesvirus-induced tumors), mucosal immunity, and vaccine development. In poultry immunology and translational research, chicken IL-21 is studied as a biomarker of T cell–dependent B cell help and germinal center–like responses and as an indicator of adaptive immune competence in infectious disease and vaccination models.