The present study was undertaken to evaluate the radioprotective effect of meso-zeaxanthin, a xanthophyll carotenoid with profound antioxidant activity. Swiss albino mice were treated with different doses of meso-zeaxanthin (50 and 250 mg/kg body weight, orally) five days before irradiation and sacrificed at different time points. The protective effects of meso-zeaxanthin on mortality, haematological parameters, bone marrow cellularity and gastrointestinal system of irradiated mice were studied. The anti-genotoxic action of meso-zeaxanthin was studied by measuring micronuclei formation, chromosomal aberrations and DNA damage (comet assay). Meso-zeaxanthin administration significantly increased the lifespan of irradiated mice and reduced myelosuppression as evident from increases in white blood cell counts, bone marrow cellularity and the number of maturing monocytes when compared to the myelosuppression in radiation control animals. Meso-zeaxanthin significantly elevated the radiation-induced reduction in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione in both liver and intestinal mucosa. The carotenoid-treated animals showed a profound reduction in genotoxic activity which was apparent in decreases in micronuclei formation and chromosomal aberrations. Irradiation also induced damage to cellular DNA as was obvious from increases in comet parameters like tail DNA%, tail moment, tail length and Olive tail moment in the radiation control group. These parameters were decreased by meso-zeaxanthin treatment. Results indicated a radioprotective potential of meso-zeaxanthin.