Zebrafish (Danio rerio) and Three-Spined Stickleback (Gasterosteus aculeatus) possess IL-4/13–like cytokines that are functional homologs of mammalian IL-4 and IL-13 and share highly conserved structural and functional features between these teleost species. Due to ancestral genome duplication events in ray-finned fish, both zebrafish and stickleback encode IL-4/13A and IL-4/13B paralogs, which collectively mediate type 2–like immune responses. These cytokines signal through receptor complexes homologous to IL-4Rα/IL-13R–type chains and activate STAT6-dependent pathways, promoting alternative (M2-like) macrophage polarization, modulation of pro-inflammatory cytokine production (e.g., il1b and tnfa), enhancement of epithelial barrier function, and support of tissue repair processes. In both species, IL-4/13–like cytokines are induced during helminth infection, mucosal inflammation, and tissue injury, where they contribute to immune regulation and resolution of inflammation. Zebrafish and stickleback are widely used models in immunology, evolutionary biology, and host–parasite interaction studies, and characterization of their IL-4/13–like signaling pathways provides insight into the evolutionary origins of Th2-type immunity. As conserved regulators of type 2–associated immune responses, IL-4/13–like cytokines in these species support comparative research into macrophage plasticity, mucosal immunity, and cytokine network evolution relevant to vertebrate inflammatory and allergic diseases.