Primary peritoneal mast cells (PeMCs) are mature connective tissue-type mast cells resident in the peritoneal cavity, readily obtained by peritoneal lavage. They originate from hematopoietic stem cells in the bone marrow and migrate as progenitors to peripheral sites, where they complete their maturation. PeMCs are characterized by abundant cytoplasmic granules containing high levels of histamine, heparin, and neutral proteases such as tryptase and chymase. As serosal-type mast cells, they play pivotal roles in innate and adaptive immunity, host defense against bacteria and parasites, and inflammatory disorders. Upon activation via IgE- or IgG-mediated mechanisms, PMCs degranulate to release preformed mediators including histamine, TNF-α, and proteases, while also synthesizing lipid mediators, chemokines, and cytokines. Unlike immature bone marrow-derived mast cells (BMMCs), PeMCs are fully differentiated and exhibit distinct functional properties, including robust responses to IgG immune complexes. Due to their mature phenotype and relative ease of isolation, primary PeMCs serve as an invaluable ex vivo and in vitro model for studying mast cell biology, particularly in the context of allergic and inflammatory diseases. Importantly, PeMCs display phenotypic and functional heterogeneity compared to mast cells from other anatomical sites, underscoring the influence of the local microenvironment on mast cell maturation and function.