Osteoprotegerin is a recently identified inhibitor of bone resorption. Recent studies indicate that osteoprotegerin also acts as an important regulatory molecule in the vasculature. The purpose of this study was to investigate the relationship between plasma osteoprotegerin levels and endothelium-dependent arterial dilation in type 2 diabetic patients. The study subjects included 40 newly diagnosed type 2 diabetic patients and 46 healthy subjects. All patients were given insulin therapy for 6 months. Plasma osteoprotegerin concentration was measured in duplicate by a sandwich enzyme-linked immunosorbent assay method, and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual glyceryltrinitrate. The plasma osteoprotegerin level in patients before treatment was 3.36 +/- 0.32 ng/l, which was significantly higher than that in control subjects (2.38 +/- 0.25 ng/l, P < 0.001). After 6 months of treatment, osteoprotegerin levels decreased markedly (2.83 +/- 0.34 ng/l, P < 0.001). Flow-mediated endothelium-dependent arterial dilation in patients before treatment was 3.21 +/- 0.52%, which was significantly lower than that in control subjects (4.46 +/- 0.56%, P < 0.01), and it improved markedly after 6 months of treatment (4.03 +/- 0.49%, P < 0.01). In multivariate analysis, osteoprotegerin was significantly associated with endothelium-dependent arterial dilation, fasting blood glucose (FBG), HbA(1c) (A1C), and ultrasensitive C-reactive protein (CRP) at baseline (P < 0.01). The absolute changes in osteoprotegerin showed significant correlation with changes in endothelium-dependent arterial dilation, FBG, A1C, and CRP in diabetic patients during the course of treatment (P < 0.01). This study shows that plasma osteoprotegerin levels are elevated in newly diagnosed diabetic patients and are significantly associated with endothelial function.