OBJECTIVE Subcutaneous insulin is absorbed at different rates from different anatomical regions, but it is not clear how much the varying rates of absorption affect plasma glucose concentrations in diabetic subjects. To address this issue, subcutaneous injections of insulin in the abdomen were compared with subcutaneous injections of insulin in the thigh. RESEARCH DESIGN AND METHODS In a crossover trial, 22 type I diabetic subjects received, in random order, a test dose of regular insulin injected subcutaneously in the abdomen on one morning and in a thigh on another morning. The subjects also received, in random order, usual morning doses of NPH and regular insulins injected subcutaneously in the abdomen on one morning and in a thigh on another morning. The study was performed in the University of Minnesota General Clinical Research Center. Main outcome measures were plasma glucose and serum free insulin. RESULTS After injections of regular insulin in the abdomen, the peak postprandial increment in plasma glucose was 3.1 mM or 29% lower (P < 0.001), the peak increment in serum free insulin was 54 pM or 38% higher (P = 0.017), and the length of time required to achieve peak serum free insulin was significantly shorter than after injections of regular insulin in the thigh. After injections of NPH and regular insulins in the abdomen, the morning peak increment in plasma glucose was 2.5 mM or 18% lower (P = 0.008) than after injections of NPH and regular insulins in a thigh. However, no significant difference was observed in the afternoon peak increment in plasma glucose. CONCLUSIONS A subcutaneous injection of regular insulin in the abdomen produced a substantially greater reduction in plasma glucose than an injection of regular insulin in the thigh. Changing the injection site of regular insulin from the abdomen to the thigh had an effect equivalent to reducing the dose administered. With injections of NPH and regular insulin in combination, the influence of the region used for injection was less but still potentially important.