Zebrafish (Danio rerio) Interleukin-6 (IL-6) is a conserved pro-inflammatory cytokine that plays a central role in regulating innate immune responses and inflammation in teleost fish. Although structurally distinct from mammalian IL-6, zebrafish IL-6 functions through gp130-associated receptor complexes to activate JAK/STAT3 signaling pathways, promoting expression of acute-phase genes, leukocyte recruitment, and inflammatory mediators. IL-6 is rapidly induced in response to bacterial infections (e.g., Mycobacterium marinum, Streptococcus spp.), viral challenges, tissue injury, and environmental stress, where it contributes to macrophage and neutrophil activation and coordination of systemic immune responses. Due to the optical transparency of zebrafish larvae and the availability of transgenic and gene-editing tools, zebrafish IL-6 has been extensively studied in models of infection, wound healing, cancer, metabolic disease, and neuroinflammation. Dysregulated IL-6/STAT3 signaling has been linked to chronic inflammation and tumor progression in zebrafish cancer models. As a key biomarker and functional mediator of inflammation, zebrafish IL-6 supports high-throughput drug screening, genetic studies of immune regulation, and comparative immunology research, reinforcing the zebrafish as a powerful vertebrate model for investigating cytokine biology and inflammatory disease mechanisms.