To the best of our knowledge, we show for the first time that a high on-aspirin residual platelet reactivity based on CEPI PFA-100 method in both T2DM and HC patients is associated with a reduced activity of the extracellular SOD, a major extracellular antioxidant enzyme deeply involved in modulating the cell redox status and highly expressed in blood vessels, particularly in arterial walls where it represents up to 70% of the total SOD activity [41]. The gene discussed is SOD1; the disease is type 2 diabetes mellitus.