The melanocortin (MC) system is composed of melanocyte-stimulating hormone, adrenocorticotropic hormone and their receptors. The MC system has a role in both pigmentation and the regulation of energy homeostasis, in which MC4R, one of the five MC receptors, has a key role. Interestingly, the barfin flounder (Pleuronectiformes) reared with a black background shows retarded growth compared to white background-reared fish, which could be associated with the MC system because of its dual role in regulating pigmentation and energy status. Here, we cloned MC4R and assessed the effects of feeding status on its expression in barfin flounder. Barfin flounder MC4R was composed of 325 amino acids and showed the highest sequence identity to MC4R of fugu (85%), followed by rainbow trout (82%), zebrafish (79%), goldfish (78%), dogfish (71%), chickens (67%), humans (67%) and mice (65%). Among 18 different tissues examined, the predominant expression of MC4R was observed in the brain, liver, testis and ovary as detected with reverse transcription PCR. Food deprivation resulted in a 4-fold increase in the number of MC4R transcripts in the liver, whereas no change was observed in the brain between fasted fish and fed controls. These results suggest that the MC system including MC4R is associated with energy homeostasis in barfin flounder and that peripheral tissues could play a role in this regulation.