OBJECTIVE Statins, in addition to cholesterol lowering, have nonlipid effects on formation and progression of atheromatous plaque. Insulin resistance and hyperinsulinemia may have detrimental influences on the arterial wall. Statins (may also) inhibit insulin signal transferring in vascular smooth cell cultures. However, their effect on insulin sensitivity remains controversial. Therefore, we decided to investigate the effect of simvastatin on insulin sensitivity in hypercholesterolemic patients. METHODS Eighteen patients with primary hypercholesterolemia were divided into simvastatin group (n = 9; 4 females, 5 males; BMI 30.6 +/- 4 kg/m2; mean ages 57 +/- 6 years) and placebo group (n = 9; 4 females, 5 males; BMI 28 +/- 2.9 kg/m2; mean ages 49 +/- 10 years). Simvastatin (20 mg/day) or placebo were given for 2 months. Total and HDL cholesterol were measured and LDL cholesterol was calculated by Friedewald formula. Insulin sensitivity was determined by using euglycemic hyperinsulinemic clamp technique [40 microU/m2/min insulin infusion rate; glucose disposal rate (M)= mg/kg/min] before and after treatment. RESULTS Plasma levels of total, LDL and HDL cholesterol decreased significantly in simvastatin group after treatment (p = 0.000, p = 0.000, and p = 0.048, respectively). Plasma levels of total cholesterol decreased significantly (p = 0.032), whereas LDL and HDL levels remained unchanged in placebo group. M value (mg/kg/min) decreased insignificantly in simvastatin group (4.32 +/- 1.57 vs. 3.71 +/- 1.91) and increased in placebo group (3.55 +/- 1.91 vs. 3.95 +/- 0.95). CONCLUSIONS Short-term simvastatin treatment did not affect insulin sensitivity determined by "gold standard" euglycemic hyperinsulinemic clamp method in hypercholesterolemic patients in this research. Further studies with simvastatin using higher doses and longer duration should be performed.