Here, we reported in vivo and in vitro that GLP-1R agonist liraglutide could protect against oxidized LDL-induced endothelial dysfunction, including enhancing vasodilatory response to acetylcholine, increasing NO bioavailability, and reducing oxidative stress, inflammation, and apoptosis, and the salutary effects of liraglutide were partly associated with GLP-1R dependent downregulation of the LOX-1/NOX4/NF-κB pathway. This evidence concerns the gene OLR1 and endothelial dysfunction.