Soluble epoxide hydrolase (sEH) is widely distributed in mammalian tissues. Epoxyeicosatrienoic acids (EETs), as metabolites of arachidonic acid, are degraded by sEH. EETs may function as antihypertensive and antiarthrosclerotic mediators for vasculature. Therefore, sEH is closely related with cardiovascular diseases and inflammation. Recent studies indicate that sEH is also involved in the regulation of lipid metabolism, and different functions of its C-terminal epoxide hydrolase domain and N-terminal phosphatase domain are revealed. Here we review the progress on the aspects of the different enzyme activity of the two terminals of sEH and the mechanisitic study on the regulation of lipid metabolism by sEH.