**1. Introduction**

Macrophages are specialized immune cells found in all body organs, whose role is to phagocytose antigens, foreign material, cancer cells, and cellular debris [1]. In addition to their primary role in regulating the innate immune response, tissue macrophages keep tissue homeostasis and niche-specific functions. The first report describing the presence of macrophages in the gut muscularis propria (MMs) was performed [2, 3] by Mikkelsen in 1980. This report identified MMs as "macrophagelike cells" based on their peculiar morphologic features [4]. The same authors concluded later that MMs, with their irregular stellate shape, represent a specialized type of macrophages, distinct from most resident tissue macrophages [5]. The gastrointestinal (GI) tract contains a heterogeneous population of tissue macrophages, most of which lie within the mucosa, where they phagocytose bacterial antigens [6] and constitute the first layer of defense against external pathogens. MMs are localized within the smooth muscle layers and are closely associated with cells essential for GI motility [7]. Due to this spatial relationship, MMs can regulate gut peristalsis by secreting chemokines, partially in response to microbial stimulation [8, 9]. This chapter will highlight the complex role of MMs in regulating GI homeostasis and functional diseases.
