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This study examined the chemopreventive effect of Nigella sativa and some of its antioxidant constituents on a number of colon cancer biomarkers in rats induced with azoxymethane (AOM). Sixty male Sprague‐Dawley rats were randomly assigned into ten subgroups: vehicle (1–5) and experimental (6–10). The rats in each group were fed one of the following diets: basal diet, (200 mg/kg) Nigella sativa, (0.2 mg/kg) selenium, (1.2 mg/kg) all‐trans‐retinol plus (100 mg/kg) dl‐α‐tocopherol and (10 mg/kg) thymoquinone, respectively. Only rats in subgroups 6–10 were injected with AOM (15 mg/kg) once per week for 2 weeks. Both groups were fed their respective diets for 5 weeks. Then they were killed and examined for colonic aberrant crypt foci (ACF). Our result showed that only vitamin supplementation was effective on ACF. Nigella sativa revealed inhibitory effects only on DNA damage (day 34) in the AOM‐treated …