Aim: This study was designed to evaluate the efficacy of evening primrose oil (EPO) on colonicanastomosis.Methods: Sixty rats with colonic anastomosis were randomly divided into six groups. EPO and 5-Fluorouracil (5-FU) were administered at doses of 5 g/kg/day and 20 mg/kg/day, respectively. Group1 served as sham control. The rats in Group 2 (EPO) received EPO (14 days preoperatively), in Group3 (Extended EPO) received EPO (14 days preoperatively and 7 days postoperatively), in Group 4 (5-FU) received intraperitoneally 5-FU (5 days preoperatively), in Group 5 (5-FU+EPO) received EPO(14 days preoperatively), and 5-FU (5 days preoperatively), in Group 6 (5-FU+ extended EPO)received EPO (14 days preoperatively and 7 days postoperatively) and 5-FU (5 days preoperatively).Histopathological examination, bursting pressure, and hydroxyproline content were used forevaluation.Results: Significant differences were found between the Groups 1, 2, and 3 and Groups 4, 5, and 6in bursting pressures. Polymorphonuclear leukocyte (PMNL) and lymphocyte infiltration wassignificantly less in group 3, compared to the control and group 2. The least PMNL infiltration wasin group 6 compared to groups 4 and 5. The hydroxyproline level was different in group 3 comparedto the control and group 2. Furthermore, groups 5 and 6 were different compared to group 4.Conclusion: EPO had favorable effects on colonic anastomosis even in groups where 5-FU wasused.