SummarySeveral studies in vitro and in vivo suggest that the nitric oxide (NO) production is impaired in diabetes mellitus. Reduced levels of NO could contribute to vascular alteration facilitating platelet-vascular wall interaction, adhesion of monocytes to endothelium, vascular smooth muscle proliferation and by decreasing endothelium-dependent vasodilation. In this study we evaluated the activity of the constitutive nitric oxide synthase (cNOS) in platelets of patients with insulin-dependent diabetes mellitus (IDDM) and with non-insulin-dependent diabetes mellitus (NIDDM). When compared to that of normal subjects, cNOS activity is significantly lower in patients with IDDM and with NIDDM (1.57 ± 0.25 vs. 0.66 ± 0.10 fmol/min/10 9 PLTs and 1.57 ± 0.25 vs. 0.67 ± 0.08, respectively; p <0.005). These data demonstrate that the platelet cNOS activity is decreased in diabetes mellitus.