Large interventional studies have shown that statins may reduce the incidence of type 2 diabetes mellitus. However, it is uncertain whether short-term statin therapy can affect insulin sensitivity in patients with the metabolic syndrome. We evaluated the effect of atorvastatin(10 mg/day) in 10 insulin-resistant subjects(age 40±12 years, body mass index 33.6±5.2 kg/m2, triglycerides 2.84±1.99 mmol/L[249±175mg/dl], glucose 6.06±0.67 mmol/L[109±12 mg/dl]) using the homeostasis model assessment(HOMA) index(parameter of insulin resistance derived from fasting glucose and fasting insulin concentrations; 5.7±2.6) in a randomized placebo-controlled, double-blind, crossover study. Subjects were randomized to receive placebo or atorvastatin, each given for 6 weeks separated by a 6-week wash-out period. At the beginning and end of each treatment phase, the patients underwent an oral glucose tolerance test, a 72-hour continuous glucose measurement, and a detailed lipid determination, including a standardized fat tolerance test. Compared with placebo, atorvastatin resulted in a significant(p=0.05) reduction in the HOMA index(-21%), fasting C-peptides(-18%), glucose(area under the curve during the oral glucose tolerance test,-7%), and a borderline(p=0.08) reduction of insulin(-18%). The parameters derived from the continuous 72-hour glucose monitoring did not change. A significant reduction also occurred in the total and low-density lipoprotein cholesterol concentrations, although the fasting and postprandial triglyceride concentrations did not change significantly. However, we found a significant correlation between atorvastatin-induced changes in the HOMA and baseline HOMA and between the atorvastatin-induced changes in triglycerides and insulin concentrations. The free-fatty acid, interleukin-6, and high sensitivity C-reactive protein concentrations did not change. Our data indicated that in insulin-resistant, nondiabetic subjects, 6 weeks of atorvastatin(10 mg/day) resulted in significant improvement in insulin sensitivity. Large interventional studies have shown that statins may reduce the incidence of type 2 diabetes mellitus. However, it is uncertain whether short-term statin therapy can affect insulin sensitivity in patients with the metabolic syndrome. We evaluated the effect of atorvastatin (10 mg / day ) in 10 insulin-resistant subjects (age 40 ± 12 years, body mass index 33.6 ± 5.2 kg / m2, triglycerides 2.84 ± 1.99 mmol / L [249 ± 175 mg / dl], glucose 6.06 ± 0.67 mmol / L [109 ± 12 mg / dl]) using the homeostasis model assessment (HOMA) index (parameter of insulin resistance derived from fasting glucose and fasting insulin concentrations; 5.7 ± 2.6) in a randomized placebo-controlled, double-blind, crossover study. Subjects were randomized to receive placebo or atorvastatin, each given for 6 weeks separated by a 6-week wash-out period. At the beginning and end of each treatment phase, the patient underwent an oral glucose tolerance test, a 72-hour continuous glucose measurement, and a detailed lipid determination, includ Compared with placebo, atorvastatin resulted in a significant (p = 0.05) reduction in the HOMA index (-21%), fasting C-peptides (-18% oral glucose tolerance test, -7%), and a borderline (p = 0.08) reduction of insulin (-18%). The parameters derived from the continuous 72-hour glucose monitoring did not change. and low-density lipoprotein concentrations did not change significantly. However, we found a significant correlation between atorvastatin-induced changes in the HOMA and baseline HOMA and between the atorvastatin-induced changes in triglycerides and insulin concentrations . The data for that in insulin-resistant, nondiabetic subjects, 6 weeks of atorvastatin (10 mg / day) res ulted in significant improvement in insulin sensitivity.