Guinea Pig (Cavia porcellus) Leukemia Inhibitory Factor (LIF) is a multifunctional cytokine belonging to the IL-6 family—which includes IL-6, IL-11, oncostatin M (OSM), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine factor 1 (CLCF1), and IL-27—and signals through receptor complexes containing the shared gp130 subunit. In guinea pigs, LIF binds to the LIF receptor (LIFR) in association with gp130, activating JAK/STAT3, MAPK, and PI3K signaling pathways that regulate cell survival, differentiation, immune modulation, and tissue repair. Guinea pig LIF is implicated in reproductive biology, including endometrial function and embryo implantation, as well as in hematopoiesis and neural cell maintenance. In infectious disease research, particularly in well-established guinea pig models of tuberculosis, influenza, and other respiratory pathogens, LIF-mediated STAT3 signaling may influence lung inflammation, tissue remodeling, and immune regulation during chronic infection. Dysregulated LIF expression could contribute to fibrosis, granuloma dynamics, or tumor progression in experimental systems. As guinea pigs are valuable translational models for respiratory disease and reproductive biology, characterization of guinea pig LIF supports investigations into IL-6 family cytokine signaling, host–pathogen interactions, stem cell regulation, and development of targeted STAT3-modulating therapies relevant to human inflammatory and fibrotic diseases.