Abstract: Transcriptome analysis of yellow catfish (Pelteobagrus fulvidraco) by RNA-seq method extracting gastrointestinal mucosa Total RNA was studied in this paper. The fish were fed with oxidized fish oil and fish oil respectively for 7d. Differential expression of genes related to melanin synthesis, melanosomes movement, melanocyte stimulating hormone-α pathway and three signal pathways controlling melanocyte differentiation were analyzed. The results showed that there were metabolic networks of melanocyte differentiation and development, melanin synthesis and regulation in the gastrointestinal mucosa. The genetic information of key enzymes and protein of melanin synthesis were introduced with plotting metabolic networks graph. The melanin content was deficient because of the genes expression level were significantly down-regulation related to controlling melanin synthesis after fed with oxidized fish oil. While melanocyte differentiation and development were improved because of the genes expression level were significantly up-regulation related to melanocyte stimulating hormone-α pathway (α-MSH). In the same time, genes expression level of WNT/β-catenin, EDN3 / EDNRB and KIT/KITL signal pathways were different. In conclusion, feeding oxidized fish oil affected melanocyte differentiation and development and reduced melanocyte number which benefited to maturity in yellow catfish. Insufficient melanin biosynthesis also led to body color variation of yellow catfish.