Functional foods include antioxidant nutrients which may protect against many human chronic diseasesby combating reactive oxygen species (ROS) generation. The purpose of the present study was to investigatethe protective effect of pomegranate peel extract (PPE) on azoxymethane (AOM)-induced colon tumorsin rats as an in vivo experimental model. Forty Sprague-Dawley rats (4 weeks old) were randomly dividedinto 4 groups containing 10 rats per group, and were treated with either AOM, PPE, or PPE plus AOM orinjected with 0.9% physiological saline solution as a control. At 8 weeks of age, the rats in the AOM andPPE plus AOM groups were injected with 15 mg AOM/kg body weight, once a week for two weeks. After thelast AOM injection, the rats were continuously fed ad-libitum their specific diets for another 6 weeks. At theend of the experiment (i.e. at the age of 4 months), all rats were killed and the colon tissues were examinedmicroscopically for lesions suspected of being preneoplastic lesions or tumors as well as for biochemicalmeasurement of oxidative stress indices. The results revealed a lower incidence of aberrant crypt foci inthe PPE plus AOM administered group as compared to the AOM group. In addition, PPE blocked theAOM-induced impairment of biochemical indicators of oxidative stress in the examined colonic tissuehomogenates. The results suggest that PPE can partially inhibit the development of colonic premalignantlesions in an AOM-induced colorectal carcinogenesis model, by abrogating oxidative stress and improvingthe redox status of colonic cells.