Tibetan sheep is one of China’s three coarse-wool sheep, the wool is mainly used for the production of Tibetan carpets and its coat color as one of important economic traits which can affect wool price directly. In this study, to investigate the functional roles of genes in Tibetan sheep skin with different coat colors, we sequenced genes from six skin samples using Solexa sequencing. The RNA-Seq analysis generated 63,283,784 and 63,644,062 clean reads in black and white skin, respectively. A total of 60 differentially expressed genes (DEGs) were identified, providing evidence that the different coat color skin changed considerably. Among these differentially expressed genes, there were 18 up-regulated genes and 42 down-regulated genes in black skin tissue. Further analysis showed that these genes involved a series of biological processes such as “pigment biosynthetic process” and “pigment metabolic process”. KEGG pathways were analyzed for the differentially expressed genes and show that Melanogenesis signaling pathway may affect the process of coat color formation. Quantitative PCR confirmed differential expression of thirteen genes, TYR, TYRP1, TYRP2, MITF, β-catenin, Wnt3a and so on. These results will expand our understanding of the complex molecular mechanisms of coat color in Tibetan sheep and provide a foundation for future studies.