Abstract: The aim of the present study was to assess plasma endothelin-1 (ET-1) and Nitric Oxide (NO) levels in children with Insulin-dependent Diabetes Mellitus (IDDM) and their relation to the degree of metabolic control and disease duration. The study group consisted of 34 children with IDDM and 17 healthy controls of matched age and sex, recruited from the Pediatric Endocrinology and Diabetes Unit; Mansoura University Children`s Hospital, Egypt, during the period January to March, 2005. Plasma ET-1 and NO levels were assessed by enzyme immunoassay and we evaluated their possible relation with metabolic control and disease duration. Plasma ET-1 levels were significantly higher in diabetic patients compared to controls, (p = 0.02). Patients with poor or moderate metabolic control had significantly higher levels of ET-1 compared to those with ideal control (p = 0.004 and 0.001), respectively. A +ve significant correlation was found between plasma ET-1 levels and NO, HbA1c levels and disease duration, (p = 0.004, 0.001 and 0.02), respectively. Although plasma NO levels in diabetic patients were not significantly different from controls, yet they were significantly higher in patients with poor metabolic control compared to those with ideal control (p<0.001). In children with IDDM, poor metabolic control and increased disease duration are associated with increased ET-1 production, which may be related to future diabetic complications. The elevated plasma NO levels in poorly controlled patients may suggest a compensatory protective response towards increased ET-1 production.