The involvement of estrogen, the female sex hormone, in a variety of gastrointestinal conditions has been documented. We studied the effect of endogenous and exogenous estrogen (estradiol benzoate, 30μg/kg/day S.C) for 8 weeks on early preneoplastic markers induced by the intraperitoneal injection of 1,2-dimethylhydrazine (20 mg/kg) in female rats. Either in sham rats or estradiol benzoate administered animals, estrogen abrogated tumor markers (CA 19.9 and CEA), decreased damage and inflammatory cells infiltration in colon tissue, attenuated oxidative stress markers (MDA, SOD, CAT, and GSH) and inflammatory mediators (IL-6 and IL-10).  In conclusion, the estrogen protects against colon injury by reducing precancerous colonic lesions and oxidative stress. The research sheds new light on the therapeutic benefits of estrogen against colon injury in rats.