Objective:To investigate the effects of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibitor, on adiponectin and markers of endothelial function in apolipoprotein E -deficient mice at an early stage of atherosclerosis.Methods: Twenty-four 6-week old male apoE-deficient mice were randomly divided into two groups: control group (normal saline) and treatment group (simvastatin (5 mg/(kg·d)). Simvastatin was administered to treatment group mice by gavage and the same volume of normal saline was administered to control group mice by the same method for 4 weeks. Total cholesterol (TC), superoxide dismutase (SOD), malondialdehyde (MDA), and nitric oxide (NO) were measured by biochemical analysis, and adiponectin was measured by an ABC-ELISA method. Results : There was no significant difference in serum TC between control and treatment groups. Compared with the control animals, simvastatin-treated animals exhibited a significant increase in serum levels of adponectin, SOD and NO, and decrease in serum MDA (P <0.01).Conclusion: Simvastatin protects endothelial function by increasing serum adiponectin, which may increase serum SOD and NO, and decrease serum MDA. This study suggests that simvastatin has therapeutic advantages, unrelated to its cholesterol-lowering effect, that are mediated by adiponectin.