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Recent studies show increased activity of soluble epoxide hydrolase (sEH) during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with<jats:italic>trans<\/jats:italic>-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (<jats:italic>t<\/jats:italic>-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndrome<jats:italic>in vivo<\/jats:italic>including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. 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