Zebrafish Interleukin-34 (IL-34) is a cytokine involved in regulating innate immune responses and macrophage development in zebrafish (Danio rerio). IL-34 is produced by various cell types, including epithelial and stromal cells, in response to immune stimulation or tissue signals. Zebrafish IL-34 functions primarily as a ligand for the colony-stimulating factor-1 receptor (CSF1R), activating intracellular signaling pathways such as ERK, JAK–STAT, and PI3K–AKT that promote survival, proliferation, and differentiation of monocytes and macrophages. Through these pathways, IL-34 contributes to the development and maintenance of tissue-resident macrophages and microglia, playing an important role in immune surveillance and inflammatory regulation during development and in adult tissues. In zebrafish, IL-34 is particularly important for early macrophage lineage development and microglial colonization of the brain. In cell culture, recombinant zebrafish IL-34 is used to promote macrophage differentiation and survival and to support functional studies of macrophage and microglial biology in in vitro immune and developmental research models.