Glucose‐lowering mechanism by clofibrate was studied in non‐insulin dependent diabetics managed with dietary therapy alone. Clofibrate 1500 mg was administered for 1 month to 15 patients, and 75 g oral glucose tolerance test and insulin tolerance test were carried out before and after 1 month of the treatment. Fasting plasma glucose values were decreased from 9.34 +/‐ 0.53 mmol/l to 7.58 +/‐ 0.33 mmol/l (P less than 0.01), and fasting insulin levels were decreased from 13.8 +/‐ 1.7 microunits/ml to 10.1 +/‐ 1.5 microunits/ml (P less than 0.05). However, insulinogenic index and sigma IRI/sigma glucose ratio during 75 g oral glucose tolerance test were not changed. Enhanced glucose fall in insulin tolerance test was also observed. As these results suggested the enhanced tissue sensitivity to insulin, we examined the insulin binding to erythrocytes before and at 3 months' treatment of clofibrate in 10 non‐insulin dependent diabetics. Insulin bindings were increased from 3.41 +/‐ 0.17% to 4.11 +/‐ 0.20% in the presence of 1 ng/ml of native insulin (P less than 0.01). This increased binding was due to an increased affinity without a change in the number of insulin receptors. These results suggest that improved glucose tolerance by clofibrate might be derived from the enhanced tissue sensitivity to insulin, probably through an enhanced affinity of insulin receptors.