Fibronectin is a high molecular weight alpha-2-glycoprotein. Its peculiar role in the structure of connective tissue, together with its wide involvement in coagulative dynamics, justified the increasing interest for fibronectin in the pathogenesis of diabetic disease and its vascular sequelae. In the present work, we evaluated the levels of plasma fibronectin (PF) in diabetics with and without retinopathy, and studied the possible correlation between the glycoprotein and some hormonal and metabolic parameters, expression of glycometabolic balance. We examined 26 type I and 24 type II diabetics, further divided into retinopathics and not retinopathics, and 43 normal subjects. We did not find any significant difference in PF levels either between normals and diabetics, or between type I and type II patients, or between retinopathics and not retinopathics. PF was significantly correlated to age, both in normals and in diabetics. Diabetic patients showed a significant positive correlation of PF to total cholesterol (r = 0.56; p less than 0.05) and triglycerides (r = 0.36; p less than 0.05). This seems to suggest, although indirectly, the existence of a relationship between the levels of PF and the degree of large vessel involvement. No significant correlation was found with HbA1c, beta-OH, AcAc, lactate, pyruvate, C-peptide, total and free insulin or GH. We further indicated an inverse correlation between PF and plasma glucagon (IRG). Very low levels of PF are commonly associated with high IRG plasma values during acute energy deprivation such as prolonged fasting and ketoacidotic coma. Therefore, PF levels might represent an index of latent to overt energy depletion.