Objective: The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for cellular uptake of oxidized LDL-cholesterol (oxLDL) from the blood. This receptor is primarily expressed on endothelial and smooth muscle cells. LOX-1 is upregulated under atherosclerotic conditions. Aim of this study was to analyze the impact of endothelial LOX-1 overexpression on vascular function in the thoracic aorta and on metabolic parameters. Methods: LOX-1 transgenic mice (LOX-1tg) were fed for 20 weeks with standard diet (Con) or high-fat diet (FD). C57BL/6 (wild type; WT) mice served as controls. There was no difference in body weight between WT and LOX-1tg mice after 20 weeks on standard or high-fat diet. Vascular function was analyzed in the thoracic aorta using a wire-myograph. Results: The endothelium-dependent relaxation was impaired in LOX-1tg + Con, but was not further decreased after high-fat diet. The endothelium-dependent relaxation was completely blocked by the NO synthase inhibitor nitro-L-arginine methylester (L-NAME). In WT and LOX-1tg vessels, endothelium-independent relaxation was not altered on standard or high-fat diet. Organ weight of heart, kidney and liver was similar in LOX-1tg + FD and WT + FD. The absolute amount of white epididymal adipose tissue was significantly increased in LOX-1tg compared to WT. This was further increased after high-fat diet. In addition we analyzed mRNA expression of leptin, adiponectin, resistin, in white epididymal adipose tissue by RT-PCR. Leptin and(IL-6 and TNF-alpha resistin mRNA expression was increased in LOX-1tg mice + FD compared to WT. Adiponectin, TNF-alpha and IL-6 mRNA expression was unchanged. Conclusion: We conclude that LOX-1 overexpression causes functional changes in the thoracic aorta which may be influenced by the increased expression of adipokines like leptin or resistin.