Context: Considerable experimental evidence inculpates vascular endothelial growth factor (VEGF) as one of the candidate factors providing a mechanistic link between hyperglycemia and diabetic complications. Aim: The aim of the study was to assess the effect of insulin treatment and glycemic control on plasma VEGF levels in children with new-onset diabetes. Methods: This prospective study assessed the changes in plasma VEGF levels after treatment of diabetes with insulin. We also aimed to ascertain whether there was any correlation between plasma VEGF levels and simultaneous random plasma glucose. The study comprised 19 children with new-onset diabetes mellitus between the ages of 3 and 18 yr. The control group comprised 55 healthy nondiabetic children with idiopathic short stature. Results: Plasma VEGF concentrations were significantly elevated in children at diagnosis of diabetes, compared with healthy controls (P < 0.0002). Plasma VEGF levels (P < 0.01) and hemoglobin A1C (P < 0.0001) declined in diabetic children after insulin treatment. There was a highly significant correlation between reduction in plasma VEGF levels and hemoglobin A1C levels (r = 0.65, P = 0.0037). We did not find any correlation between the simultaneous plasma glucose values and basal VEGF. Conclusions: Presence of hyperglycemia and/or insulin deficiency in children with new-onset of diabetes is associated with plasma VEGF elevation, even at the outset of disease, and this can be mitigated by insulin therapy. Copyright © 2005 by The Endocrine Society.