Background: The aim of this study is to determine the effect of melatonin on intestinal anastomosis in the presence of peritonitis. Material and Methods: 32 Wistar albino rats were randomized into four groups (n = 8): A ( sham), B ( control), C ( melatonin 5 mg/kg), and D ( melatonin 10 mg/kg). In group A, only cecal dissection was carried out. In the other groups, cecal ligation and puncture (CLP) followed cecal dissection in order to induce bacterial peritonitis. 24 h after the previous operation, cecal resection and iliocolic anastomosis were performed in the rats of all groups. In group C (5 mg/kg) and group D ( 10 mg/kg), melatonin was injected for 5 consecutive days starting after CLP. At the 48th hour of the CLP procedure, blood was drawn via the tail vein for tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) analysis, and on the 4th day of the experiment relaparotomy was carried out for bursting pressure ( BP) measurements. The intestinal tissue containing the anastomotic line was then snap-frozen in liquid nitrogen and stored at -80 degrees C for determination of tissue levels of malondialdehyde (MDA) and glutathione (GSH). Results: The tissue MDA level, blood TNF-alpha and IL-6 levels of group B were significantly higher than in the other groups, whereas the BP results and GSH levels of group B were found to be significantly lower than in the other groups. The results of groups C and D are statistically different from those of group B. When we compared the results of groups C and D, we found significantly higher results in terms of BP and GSH levels in group D and also significantly lower results in terms of MDA, blood TNF-alpha and IL-6 levels in group D. Conclusion: The findings of this experiment suggest that melatonin has a dose-independent positive effect on wound healing of colonic anastomosis. Copyright (c) 2007 S. Karger AG, Basel.