Background. Anastomotic leakage is the major complication after colorectal surgery. To date, animal experiments concerning colorectal anastomosis focus on anastomotic healing instead of anastomotic leakage. This study aims to develop a new experimental model for colorectal anastomotic leakage. Methods. A control group, receiving an anastomosis with 12 interrupted sutures, was compared to a group receiving an anastomosis with 6 interrupted sutures. When the leakage rate was observed to be too low, the number of sutures was decreased stepwise, to 5 or less. Each group contained 9 "C57B16-mice". After 7 d the Anastomotic Bursting Pressure (ABP) was determined. Results. In the first experiment, one mouse (11.1%) in the case group and none in the control group developed leakage. Average ABP was 152,2 mmHg in the control group and 138,8 mmHg in the case group (P = 0,111). In the second experiment, case group receiving an anastomosis with 5 sutures, 4 mice (44.4%) in the case group developed leakage. This experiment was repeated twice resulting in leakage rates of 33.3% and 44.4%. The average overall ABP in the case group was 142,7 mmHg vs. 179,9 mmHg (P = 0,022) in the control group. The mice without leakage showed a stabilization of average weight loss around day 2 and 3 and a decrease afterwards. The mice with leakage showed a decrease only after day 5. The difference in wellness-scores between the groups with- and without leakage was 2 points, increasing during follow-up. Conclusions. The model of anastomotic leakage caused by creating an anastomosis with 5 interrupted sutures is feasible. Weight loss and wellness-scores are good predictors of leakage. 2009 Elsevier Inc. All rights reserved.