Endothelial dysfunction is frequently found in diabetic subjects. This study was performed to investigate whether atorvastatin therapy was able to reverse endothelial dysfunction in type 2 diabetes and, if so, whether the effect was due to its antiinflammatory action. Eighty patients (baseline low density lipoprotein, 4.37 +/- 0.71 mmol/liter) were randomized to atorvastatin (10 mg daily for 3 months, followed by 20 mg daily for 3 months) or placebo in a double blind study. Endothelial function was assessed by high resolution vascular ultrasound, and high sensitivity C-reactive protein (CRP) was assessed by immunoturbidimetric assay. Diabetic patients had higher CRP (P < 0.01) than matched nondiabetic controls, and both endothelium-dependent and independent vasodilation were impaired (P < 0.01). Atorvastatin (10 and 20 mg) lowered plasma cholesterol by 32.9% and 38.0%, triglyceride by 15.4% and 23.1%, and low density lipoprotein by 43.4% and 50.1%, respectively. At 6 months, plasma CRP decreased in the atorvastatin group compared with baseline (P < 0.05). Endothelium-dependent vasodilation improved in the atorvastatin group compared with the placebo group (P < 0.05). The percent change in endothelium-dependent vasodilation at 6 months correlated with the percent change in CRP (r = -0.44; P < 0.05), but not with changes in plasma lipids. In conclusion, treatment with atorvastatin in type 2 diabetes led to a significant improvement in endothelium-dependent vasodilation, which might be partly related to its anti-inflammatory effect.