The soluble epoxide hydrolase (sEH) is a fatty acid epoxide metabolizing enzyme and its deletion and/or inhibition has been linked with increased levels of epoxyeicosatrienoic acids and altered cardiovascular homeostasis.The morpholino (MO) mediated downregulation/ inhibition of the sEH in zebrafish results in a defective caudal vein plexus (CVP) as well as reduced numbers of hematopoietic stem and progenitor cells (HSPC). A screen of fatty acids revealed that the sEH metabolite 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME) was able to rescue HSPC numbers in zebrafish treated with the sEH inhibitor. In sEH-/- mice fewer bone marrow cells were mobilized by G-CSF than in wild-type mice and a CFU-S12 assay revealed reduced number of colonies in spleens of mice that received bone marrow cells from sEH-/- mice in comparison to cells derived from wild-type mice. 12,13-DiHOME was able to rescue this phenotype. . Thus, sEH activity regulates vascular sprouting of the CVP in zebrafish and the sEH product; 12,13-DiHOME, influences hematopoietic stem and progenitor cell function in zebrafish and mice.