Emerging research supports that soluble epoxide hydrolase (sEH), an enzyme involved in eicosanoid metabolism, could be a promising target for obesity-associated disorders. The sEH enzyme is overexpressed in many tissues of obese animals. Genetic ablation or pharmacological inhibition of sEH attenuates the development of a wide range of obesity-induced disorders, including endoplasmic reticulum stress, metabolic syndrome, kidney diseases, insulin resistance, fatty liver, hepatic steatosis, inflammation, and endothelial dysfunction. Furthermore, our recent research showed that genetic ablation or inhibition of sEH attenuated obesity-induced intestinal barrier dysfunction and its resulted bacterial translocation, which is widely regarded to be a central mechanism for the pathogenesis of various obesity-induced disorders. Together, these results support that targeting sEH could be a promising strategy to reduce risks of obesity-induced disorders, at least in part through blocking obesity-induced leaky gut syndrome.Copyright © 2020 Elsevier Ltd. All rights reserved.