Background Tissue adhesives (TAs) in gastrointestinal surgery are gradually gaining acceptance. Before implementation as colonic sealants, an evaluation of the sealing capability of a TA when in contact with fecal matter, as in a leaking anastomosis, is needed. In this study, we used clinically available TAs for the sutureless closure of colonic defects evaluating mechanical strength and tissue healing. Methods A total of 160 rats were divided into 8 groups. Two .5-cm incisions were created, one in the proximal and another in the distal colon. Incisions were sealed with a TA: Histoacryl Flex, Bioglue, Dermabond, Tissucol, Duraseal Xact, gelatin-resorcinol-formaldehyde or Glubran 2. A control group was included in which the colonic defects were not sealed. Follow-up time was 3 or 10 days. Clinical complication rate, bursting pressure, and histopathologic analysis was included. Results Leakage rates in the TA groups were highest for Duraseal Xact, Bioglue, and gelatin-resorcinol-formaldehyde at 3 and 10 days. The cyanoacrylates Glubran 2, Histoacryl Flex, and Omnex, and the fibrin glue Tissucol showed the lowest overall clinical complication rates while maintaining the highest bursting pressure at day 10. Histoacryl Flex exhibited significantly higher collagen formation at day 10 than the other TAs. Conclusions This experimental model evaluates the protective effect of a TA seal on a leaking colonic defect. We found large differences in leakage rates and inertness of the tested TAs. The cyanoacrylates Histoacryl Flex, Omnex, and Glubran 2 as well as the fibrin glue Tissucol demonstrated the lowest leakage rates and the most inert histopathologic profile while maintaining high mechanical strength.@en