Paralytic　ileus　is　common　in　patients　with　septic　shock,　causing　high　morbidity　and　mortality.　Enteric　neurons　and　enteric　glial　cells　(EGCs)　regulate　intestinal　motility.　However,　little　is　known　about　their　interaction　in　endotoxemia.　This　study　aimed　to　investigate　whether　reactive　EGCs　had　harmful　effects　on　enteric　neurons　and　participated　in　intestinal　motility　disorder　in　mice　during　endotoxemia.　Endotoxemia　was　induced　by　the　intraperitoneal　injection　of　lipopolysaccharide　(LPS)　in　mice.　Fluorocitrate　(FC)　was　administered　before　LPS　injection　to　inhibit　the　reactive　EGCs.　The　effects　of　reactive　EGCs　on　intestinal　motility　were　analyzed　by　motility　assays　in　vivo　and　colonic　migrating　motor　complexes　ex　vivo.　The　number　of　enteric　neurons　was　evaluated　by　immunofluorescent　staining　of　HuCD,　nNOS,　and　ChAT　in　vivo.　In　addition,　we　stimulated　EGCs　with　IL-1　beta　and　TNF-alpha　in　vitro　and　cultured　the　primary　enteric　neurons　in　the　conditioned　medium,　detecting　the　apoptosis　and　morphology　of　neurons　through　staining　TUNEL,　cleaved　caspase-3　protein,　and　anti-beta-III　tubulin.　Intestinal　motility　and　peristaltic　reflex　were　improved　by　inhibiting　reactive　EGCs　in　vivo.　The　density　of　the　neuronal　population　in　the　colonic　myenteric　plexus　increased　significantly,　while　the　reactive　EGCs　were　inhibited,　especially　the　nitrergic　neurons.　In　vitro,　the　enteric　neurons　cultured　in　the　conditioned　medium　of　reactive　EGCs　had　a　considerably　higher　apoptotic　rate,　less　dendritic　complexity,　and　fewer　primary　neurites.　Reactive　enteric　glial　cells　probably　participated　in　paralytic　ileus　by　damaging　enteric　neurons　during　endotoxemia.　They　might　provide　a　novel　therapeutic　strategy　for　intestinal　motility　disorders　during　endotoxemia　or　sepsis.