trans-Resveratrol, a natural occurring polyphenol, has been described as an antiproliferative and proapoptotic agent in vitro. Here, we studied the effect of trans-resveratrol administered orally at a dose of 60 mg/kg for 49 days on early preneoplastic markers induced by the intraperitoneal injection of 1,2-dimethylhydrazine (20 mg/kg). We measured trans-resveratrol and its derivates by liquid-liquid extraction followed by high-performance liquid chromatography diode array detection analysis in colon contents. Dihydroresveratrol was the most abundant compound in the colon, followed by trans-resveratrol glucuronide and small amounts of trans-resveratrol and its sulfate. The administration of trans-resveratrol decreased aberrant crypt foci by 52%, and mucin depleted foci by 45% in colon. In conclusion, the correlation between the reduction of precancerous colonic lesions and the availability of trans-resveratrol in the colon provides a new insight into the therapeutical potential of this polyphenol and its metabolites.