Objective: The aim of this study was to investigate the effect of platelet-rich plasma (PRP) on the healing of colonic anastomosis in the presence of sepsis. Materials and Method: Fifty Wistar-albino male rats were used. Ten healthy rats were euthanized to prepare PRP, the rest were subjected to colonic anastomosis and randomly allocated into four groups of 10 rats each as anastomosis without PRP (C), without PRP in sepsis (SC), anastomosis with PRP (C-PRP), and with PRP in sepsis (S-PRP). Sepsis was induced by cecal ligation and puncture procedure. All animals were euthanized on postoperative day 7. The body weight change, anastomotic bursting pressure (ABP), tissue hydroxyproline (TH) and histopathological examination of each group were analyzed by using one-way analysis of variance (ANOWA) and Tukey's HSD post-hoc test to assess the differences between the groups. Results: There was no statistical difference among the groups in terms of body weight changes. The ABP was measured at a mean value of 179.5 +/- 10.3, 129.3 +/- 14.2, 209 +/- 14.4, and 167.5 +/- 7.5mm-Hg, in group C, SC, C-PRP, and S-PRP, respectively. The ABP and TH of C-PRP group was significantly higher than three groups (p < .05, for each comparison). In sepsis, PRP significantly raised the mean ABP and TH levels up to the levels of C group. Tissue regeneration was significant with increased collagen formation in C-PRP group than the other groups (p < .05). The healing effect of PRP in the presence of sepsis was significant than S-group (p < .05), while similar to C group (p = .181). Conclusion: PRP application to colonic anastomosis promotes the healing process in rats with intra-abdominal sepsis.