The effects of intensive insulin therapy on metabolic control, fatty acid metabolism and platelet function were studied in 18 non-obese non-insulin-dependent diabetics (NIDDs) with secondary failure to oral antidiabetic drugs (OAD). Patients were randomly allocated either to continue maximal OAD (Group I, n = 9) or to receive a multiple injection regimen of insulin therapy (Group II, n = 9) for a 6-month period. At baseline both groups were identical for clinical and biological parameters. At study day 180, fasting blood glucose (P < 0.01) and mean capillary blood glucose (P < 0.05) were reduced in group II but the difference between HbA1 percentages remained non-significant. At study day 60, in total plasma lipids, oleic acid was lower (P < 0.05), linoleic acid (P < 0.05) and the sum of polunsaturated fatty acids (PUFA) (P < 0.05) were higher in group II than I. In triglycerides, palmitic acid was lower in group II at study days 60 (P < 0.01) and 180 (P < 0.05), whereas gamma-linolenic acid was decreased (P < 0.05) at study day 180 only. A similar change was noted in cholesterol esters for gamma-linolenic acid at study day 60 (P < 0.05). No difference was noted between both groups for platelet agregation, insulin sensitivity and clinical parameters despite a significant increase in body weight in group II at study day 180. Positive correlations were obtained between the content of different lipid fractions in some PUFA and the glucose clearance. We conclude that optimized insulin therapy in NIDDs with secondary failure to OAD leads to a transient improvement in glucidic and lipidic metabolism but has no significant effect upon platelet aggregation and insulin sensitivity.