BACKGROUND: Mesenchymal stem cells (MSCs) are likely involved in pathological processes of immune-related diseases, including psoriasis, because of their immunoregulatory and pro-angiogenic effects. DNA methylation plays an essential role in regulating gene expression and maintaining cell function. OBJECTIVE: This study aimed to investigate the gene methylation profile of dermal MSCs from patients with psoriasis. METHODS: We isolated and expanded dermal MSCs from psoriatic patients and normal controls using the attachment assay and conducted genome-wide DNA methylation profile and gene ontology analyses using microarray. RESULTS: The cultured cells were indentified as MSCs by surface marker and differentiation assays. The genome-wide promoter methylation profile of MSCs from psoriatic derma was markedly different from the normal derma derived MSCs. Genes involved in cell communication, surface receptor signaling pathway, cellular response to stimulus, and cell migration were differently methylated. Several aberrantly methylated genes related epidermal proliferation, angiogenesis, and inflammation were found differently expressed in psoriatic patients. CONCLUSIONS: These results indicated that the MSCs from dermal of psoriasis are probably participant in the pathogenesis and development of psoriasis through an extraordinarily complex mechanism.