The aim of our study was to evaluate proinflammatory TNF-α, Th-1- (IL-2) and Th-17- (IL1-β, IL-6, IL-9, IL-17, IL-21, IL-22, and IL-23) related cytokines, TGF-β, GM-CSF, and endothelin-1 (ET-1) in arterial and venous blood of patients affected by systemic sclerosis with and without DU and to analyze the correlations between cytokine levels and clinical scores of skin fibrosis and vascular involvement. Here, IL21 is linked to systemic sclerosis.