In this study we evaluated in vivo the tolerance induced by the combination of Se, Zn and Mn (4 microg/ml each) plus Lachesis muta venom (4 ng/ml) (O-LM) to high doses of ionizing radiation. The protective effect of O-LM was investigated on the small-intestine and bone marrow of mice irradiated with a single whole-body dose of 10 Gy employing a (137)Cs source. Mice were sacrificed 3 days after irradiation. Mice receiving a subcutaneous daily O-LM injection starting 30 days before irradiation, showed a higher number of crypts, enhanced villous conservation and lack of edema or vascular damage in comparison to the untreated and irradiated group. In addition, O-LM treatment decreased vascular damage and the grade of aplasia preserving medullar progenies induced by ionizing radiation on mouse bone marrow. The protective effect of O-LM against radiation injury to the small intestine was associated with an increase in proliferation and a reduction of apoptosis in intestinal crypts and furthermore, to an enhanced intestinal immunoreactivity of MnSOD, and CuZnSOD, and also catalase. Based on the present results and taking into account that O-LM is being safely administered in phase I clinical trial as an immunomodulator, we suggest that O-LM could be an attractive candidate as a safe radioprotective agent for patients undergoing radiotherapy.