The full-length cDNA of melanin concentration hormone receptor (MCHR) was isolated from the brain of Cynoglossus semilaevis using RACE (rapid amplification of cDNA ends) method. The spatial and temporal expression patterns of MCHR mRNA in different tissues were analyzed to link with the degree of pigmentation on the blind-side of fish by the quantitative real-time PCR. Results showed that C. semilaevis MCHR1 cDNA sequence was 1685 bp in length and contained a 642 bp of open reading frame encoding 359 amino acids. It shared 83.3% identity with Paralichthys olivaceus. Based on the phylogenetic analysis, C. semilaevis MCHR1 was clustered with the Pleuronectiformes, Cyprinodontiformes and Perciformes species. In addition, C. semilaevis MCHR2 cDNA sequence was 1626 bp in length and contained a 1044 bp of open reading frame encoding 347 amino acids. The identity was more than 90% homology to pleuronectiformes species. C. semilaevis MCHR2 was clustered with the pleuronectiformes and perciformes species based on the phylogenetic analysis. MCHR1 mRNA was mainly expressed in gill and MCHR2 mRNA was primarily expressed in the eye-side skin, followed by gonad. The spatial expression patterns of MCHR mRNA implied that MCHR regulates the physiology of C. semilaevis through endocrine, paracrine and autocrine pathways. Pituitary MCHR1 mRNA level significantly increased during the initial stage of blind-side pigmentation and peaked when fish had 50% pigmentation on the blind-side. By comparison, skin MCHR1 mRNA maintained at high levels during the pigmentation occurring on the blind-side of fish. Both pituitary and skin MCHR2 mRNA levels peaked when fish had about 10% blind-side pigmentation, then significantly decreased as the degree of pigmentation reduced. The results showed that the MCHR is directly or indirectly involved in the regulation of blind-side hypermelanosis in half-smooth tongue sole.