Short-chain fatty acids (SCFAs), 2–4 carbon monocarboxylates including acetate, propionate and butyrate, are known to have a variety of physiological and pathophysiological effects on the intestine. Previously, we reported that the SCFA receptor, G-protein coupled receptor 43 (GPR43), is expressed by enteroendocrine and mucosal mast cells in the rat intestine. In the present study, expression and localization of GPR43 were investigated in the human large intestine. Gene and protein expression of GPR43 in the human ascending colon was analyzed by reverse transcriptase/polymerase chain reaction and Western blotting, respectively. In addition, localization of GPR43 was investigated by immunohistochemistry. In RT-PCR analysis, GPR43 mRNA was detected in whole wall mRNA samples. Western blotting analysis revealed the expression of GPR43 protein in whole wall and scraped mucosa protein samples, but not in muscle or submucosa. GPR43 immunoreactivity was observed in the intracellularly in enterocytes and in the peptide YY-immunoreactive enteroendocrine cells. These results indicate that the short chain fatty acid receptor, GPR43 is expressed by enteroendocrine L cells containing peptide YY in the human large intestine.