['Colorectal anastomoses created in a contaminated environment result in a high leakage rate. This study investigated whether using anastomotic sealants (TissuCol(®), Histoacryl(®) Flex, and Duraseal(®)) prevents leakage in a rat peritonitis model.', 'Sixty-seven Wistar rats were divided into control and experimental groups (TissuCol, Histoacryl, and Duraseal groups). Peritonitis was induced 1 day before surgery with the cecal ligation puncture model. On day 0, colonic anastomosis was constructed with sutures and then sealed with no adhesive (control group) or one select adhesive (experimental groups). Bursting pressure, abscess formation, and adhesion severity were evaluated on day 3 or day 14. Hematoxylin and eosin staining and immunohistochemical staining for CD4, CD8, CD206, and iNOS were performed.', 'On day 3, bursting pressures of the TissuCol group (120.1\u2009±\u200925.3 mmHg), Histoacryl group (117.3\u2009±\u200920.2 mmHg), and Duraseal group (123.6\u2009±\u200935.4 mmHg) were significantly higher than the that of the control group (24.4\u2009±\u200931.7 mmHg, p\u2009<\u20090.001). Abscesses around the anastomosis were found in the control group (6/7) and Duraseal group (2/9) but not in the TissuCol group or Histoacryl group. A higher number of CD206+ cells (M2 macrophages), a lower number of iNOS+ cells (M1 macrophages), a higher M2/M1 index, and a higher CD4+/CD8+ index were seen at the anastomotic site in all experimental groups compared with the control group on day 3. On day 14, abscesses were only found in the control group. Adhesion severity in the Duraseal group was significantly lower than that in the control group (p\u2009=\u20090.001).'] Is the prevention of colorectal anastomotic leakage with tissue adhesives in a contaminated environment associated with the presence of anti-inflammatory macrophages?