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Introduction: Mechanical ileus is a frequent disorder seen in general surgery. While standard therapy is surgical removal of the obstacle, little is known on alterations in gut physiology during intestinal dilatation. We aimed to investigate afferent nerve sensitivity and leucocyte numbers in the intestinal wall during mechanical ileus.Methods: C57Bl6 mice were anesthetized by isoflurane inhalation. After a mini-laparotomy, the small intestine was ligated approximately 5 cm distal to the ligament of Treitz, while controls received a mini-laparotomy only. Intestinal afferent sensitivity and leucocyte infiltration into the intestinal wall were investigated in ileus animals or controls after 3, 9 and 24 hours in different subgroups (each n=6). A dilated segment of small intestine located 5 mm proximal to the ligature was prepared for multi-unit mesenteric afferent nerve and motility recordings in vitro. Histological assessment by myeloperoxidase (MPO) stains was performed on segments proximal and distal to the ligature in ileus animals. Results: Small intestinal motility in vitro was reduced in ileus segments compared to controls at all 3 time points after induction of ileus (p < 0.05). Maximum afferent firing to serosal 5-HT (500 μM) peaked at 30±3 imp sec^-1 3h after the beginning of ileus compared to 10±1 imp sec^-1 in controls (mean±SEM; p<0.001). No differences in 5-HT sensitivity were observed between segments from ileus and control animals at the 9h and 24h time point. Ileus segments were less sensitive to bradykinin (0.5 μM) compared to control segments at all time points. This difference was 32±4 imp sec^-1 following ileus compared to 42±2 imp sec^-1 in controls at 24h after the beginning of ileus (p<0.05). Continuous mechanical ramp distension of the intestinal loop was followed by a pressure dependent rise in afferent nerve discharge that was reduced in ileus segments compared to controls (p<0.05). MPO stains demonstrated a rise in leucocyte infiltration in the intestine distal to the ligature which was 191±32 cells per mm2 compared to 3±0.6 cells in the dilated proximal intestine 24 h after the beginning of ileus (p<0.01).Conclusions: Afferent nerve sensitivity is altered secondary to mechanical ileus. Reduced afferent sensitivity for bradykinin and painful distension stimuli may hint at activation of anti-nociceptive mechanisms during mechanical ileus, while the pattern of leucocyte infiltration is unclear and warrants further investigation.