Abstract <p>Arctic fox coat color varies seasonally, white in winter and gray in summer. To find out the potential effect or genes involved in this characteristic of the white morph of the arctic fox, this study utilized RNA sequencing-based transcriptome analysis to identify differentially expressed genes. Firstly, we measured and analyzed the melanin content of pelage during the two peak periods in the circannual rhythm of coat color molt in arctic fox, July and December, and found that melanin content was significantly higher in July than in December (<i>p</i> &lt; 0.01). Transcriptome sequencing was then performed on skin tissues from the middle dorsal region in July and December. A total of 1177 differentially expressed genes were detected. We also identified differential expression of several key pigmentation genes, six of which are located in the melanogenesis pathway. Six differentially expressed genes were validated by real-time quantitative PCR, and the results obtained were consistent with the transcriptome sequencing results. This study provides the molecular foundation and contributes to future studies of understanding the genic regulatory mechanism underlying seasonal coat color change in arctic fox.</p>