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Introduction: Postoperative ileus (POI) involves reflex inhibition of intestinal motility and a subsequent intestinal inflammatory response that is characterized by efferent vagal modulation. However, the role of central vagal afferents in the early phase of POI is unknown. We, therefore, aimed to explore central vagal afferent nerve activation early during POI.Material and Methods: C57BL/6 mice were vagotomized 3-4 days prior to ileus experiments, while control animals received a sham operation without vagotomy. For ileus experiments, laparotomy was either followed by standardized small bowel manipulation to induce POI or sham treatment for control. Then, after 3h or 9h, the brain was removed, fixed and Fos-immunohistochemistry was performed to determine neuronal activation in the vagal nucleus of the solitary tract (NTS) and the area postrema. Each subgroup contained an n of 6. Data were analyzed by two-way ANOVA.Results:The number of Fos-positive neurons in the NTS was 15±0.5 at 3 h following ileus which was not different from 14±0.4 in sham controls and uninfluenced by vagotomy (12±2). At 9 h after induction of POI, the number of Fos-positive neurons was increased in the NTS to 186±6 compared to 60±4 in sham controls (p<0.05) which was not different to 74±4 neurons after vagotomy (n.s.). In the area postrema, after performing a vagotomy, the number of Fos positive cells was higher during POI at 9 h compared to sham controls (14±2 in POI vs. 2±1 in sham controls, p<0.05).Conclusions:Central nerve activation in the NTS occurs via vagal afferents 9 h after induction of POI. This suggests that vagal afferents projecting to the CNS were sensitized, potentially by inflammatory mediators released in the intestinal wall. Central activation in the area postrema may be secondary to higher permeability of the blood-brain-barrier in this area, allowing access of inflammatory mediators via the systemic circulation with subsequent neuronal activation.