Metabolic syndrome is a common risk factor in chronic kidney disease. We investigated whether liraglutide [(LIRA), a glucagonlike peptide-1 receptor (GLP-1R) agonist] treatment improved renal vascular function and renal remodeling in male Zucker rats on a high-salt diet (6% NaCl). Zucker lean (1/1) and obese (fa/fa) rats (8 weeks old) were treated with vehicle or LIRA (0.1 mg/kg per day) for 8 weeks on a high-salt diet. The glomerular filtration rate (GFR) was measured at 0 and 8 weeks using the fluorescein isothiocyanate/sinistrin method in conscious rats. We used X-ray microangiography to measure renal arterial vessel diameter (70-350 mm) and vessel number in vivo in anesthetized rats. Renal protein expression levels of nitrotyrosine, CD-68, endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), transforming growth factor-b1, cyclooxygenase-2, and GLP-1R were assessed by western blotting. Renal gene expressions were determined by real-time polymerase chain reaction. In contrast to vehicletreated rats, fa/fa-LIRA rats improved GFR, nitric oxide (NO)mediated vasodilation in response to acetylcholine and sodium nitroprusside in small arterial vessels (,200 mm diameter). LIRA treatment increased vessel responsivity to NO donors in comparison with vehicle treatment. Increases in the expressions of proinflammatory, profibrotic, and oxidative stress related genes in fa/fa rats relative to 1/1 were unaltered by LIRA, other than a trend toward attenuation of VCAM-1 gene expression. However, LIRA treatment increased protein expressions of eNOS (P 5 0.014) and VEGF (P 5 0.063), while reducing glomerular macrophage infiltration in comparison with vehicle-treated fa/fa rats. Low-dose LIRA treatment improved renal vascular function through amelioration of vascular dysfunction and improved NO-mediated dilation of small intrarenal arteries and arterioles and a reduction in renal inflammation. Some of the findings from this study were part of an oral presentation entitled "Liraglutide treatment improves renal vascular function in Zucker rats as visualized by microangiography" in a symposium at the American Society of Nephrology (Kidney Week) meeting, October 30 to November 5,