Obesity-induced vascular dysfunction involves pathological remodeling of the visceral adipose tissue (VAT) and increased inflammation. Our previous studies showed that arginase 1 (A1) in endothelial cells (EC) is critically involved in obesity-induced vascular dysfunction. We tested the hypothesis that EC A1 activity also drives obesity-related VAT remodeling and inflammation. Our studies utilized wild-type and EC-A1 knockout (KO) mice made obese by high fat/high sucrose (HFHS) diet. HFHS diet induced increases in body weight, fasting blood glucose, and VAT expansion. This was accompanied by increased arginase activity and A1 expression in vascular EC and increased expression of tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), interleukin-10 (IL-10), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein in both VAT and EC. HFHS also markedly increased circulating inflammatory monocytes and VAT infiltration by inflammatory macrophages, while reducing reparative macrophages. Additionally, adipocyte size and fibrosis increased and capillary density decreased in VAT. These effects of HFHS, except for weight gain and hyperglycemia, were prevented or reduced in mice lacking EC-A1 or treated with the arginase inhibitor ABH (2-(S)-amino-6-boronohexanoic acid). In mouse aortic EC, exposure to high glucose (25 mM) and Na palmitate (200 μM) reduced NO production, increased A1, TNFα, VCAM-1, ICAM-1 and MCP-1 mRNA, and monocyte adhesion. Knockout of EC-A1 or ABH prevented these effects. Summary- HFHS diet-induced VAT inflammation is mediated by EC A1 expression/activity. Limiting arginase activity is a possible therapeutic means of controlling obesity-induced vascular and VAT inflammation.