Gut lumen is continually exposed to many agents, including noxious compounds. The intestinal epithelia form a barrier between the internal and luminal (external) environments. Chemical receptors that detect the luminal environment are thought to play an important role as sensors and as modulators of epithelial cell functions. The Molecular analysis of various epithelial cell membrane receptor proteins has elucidated the sensory role of these cells in the gut chemosensing system. Nutrient sensing systems by these receptors in the small intestinal epithelia are thought to influence nutrient metabolism and local physiological function. Much less is known, however, about the physiological roles of chemosensing in the large intestine. We have investigated the contractile and secretory effects of short-chain fatty acids (SCFAs), the primary products of commensal bacteria, and the expression of SCFA receptors in the large intestine. The findings indicate that the epithelia in the large intestine also detect and respond to luminal contents, particularly bacterial metabolites, for host defense. We recently reported that luminal bitter tastants and odorants affect transepithelial ion transport in human and rat colon, and that putative receptors are expressed in colonic mucosa. In this review, we describe the secretory effects of chemical stimuli on lumen associated with the expression pattern of sensory receptors, focusing on the large intestine.