AIM: The aim of this experimental study is the assessment of the effects of the immediate post-operative intraperitoneal administration of 5-fluorouracil and irinotecan on the healing process of large bowel anastomoses in rats.MATERIALS AND METHODS: Sixty male Wistar rats were divided into 4 groups of 15 rats each. The rats underwent large bowel resection and anastomosis, followed by the intraperitoneal administration of normal saline (group 1), 5-fluorouracil (group 2), irinotecan (group 3) or the combination of 5-fluorouracil and irinotecan (group 4). All animals were killed on the eighth post-operative day. During post-mortem examination, the anastomoses were assessed macroscopically for a possible anastomotic leak and the extent of adhesion formation. Subsequently, the anastomotic bursting pressure was measured, and the anastomoses were assessed histologically.RESULTS: No anastomotic dehiscence was observed in the rats of group 1. In groups 2 and 3, we observed 3 anastomotic leaks in each group, and in group 4, we observed 5 leaks (P = 0.111). The mean bursting pressure of the anastomoses in group 1 was significantly higher compared to groups 2, 3 and 4 (P < 0.001). The least inflammatory cell infiltration score was observed in group 1 (P < 0.001). The lowest neoangiogenesis score was observed in group 2 and the highest in group 4. The collagen formation in group 1 was significantly higher compared to the other 3 groups (P < 0.001). Similar results were observed for the fibroblast activity, where group 1 revealed significantly higher fibroblast scores compared to groups 2, 3 and 4 (P < 0.001). Finally, groups 2, 3 and 4 showed significantly lower hydroxyproline levels compared to the control group (P < 0.001).CONCLUSION: The immediate, post-operative intraperitoneal administration of 5-fluorouracil or irinotecan had a negative effect on the healing process of the large bowel anastomoses in rats. The negative effects of the combination of 5-fluorouracil and irinotecan were statistically more significant compared to the single use of 5-fluorouracil or irinotecan.