The effect of tibolone, a new therapeutic agent for menopause, on glucose and lipid metabolism was investigated in 11 healthy postmenopausal women. At baseline and after 3 months of tibolone administration (2.5 mg/day), glucose metabolism was evaluated in each subject using both an oral glucose tolerance test (75 g) and the minimal model method of a frequently sampled intravenous glucose tolerance test. Frequently sampled intravenous glucose tolerance test allows the calculation of insulin sensitivity and peripheral glucose use independent of insulin. High-density lipoprotein-cholesterol, total cholesterol, apoprotein-A, and apoprotein-B measured in fasting conditions were not modified by tibolone, whereas triglycerides were reduced significantly (P < 0.01). Fasting levels of glucose were reduced significantly (P < 0.025), whereas those of insulin, C-peptide, and the C-peptide/insulin ratio were not modified. Glucose, insulin, C-peptide, and the C-peptide/insulin ratio responses to oral or iv glucose were not modified. Insulin sensitivity was inversely correlated to body mass index, and independent on that body mass index was significantly enhanced (P < 0.01). Glucose utilization independent of insulin was not modified. The present data indicate that tibolone does not negatively influence glucose metabolism and may indeed improve both the peripheral tissue sensitivity to insulin and the lipid profile.