Enteric glial cells (EGCs) produce soluble mediators that regulate homeostasis and permeability of the intestinal epithelial barrier (IEB). We investigated the profile of polyunsaturated fatty acid (PUFA) metabolites produced by EGCs from rats and from patients with Crohn’s disease (CD), compared with controls, along with the ability of one of these metabolites, 15-hydroxyeicosatetraenoic acid (15-HETE), to regulate the permeability of the IEB.