An immunomodulator ginsan, polysaccharide isolated from Panax ginseng, showed a mitogenic activity, generation of LAK cells, and the secretion of several cytokines. In the present study, we evaluated the protective effects of in vivo injected ginsan against irradiation. Ginsan was found to significantly increase the number of bone marrow cells, spleen cells and the number of circulating neutrophils, lymphocytes and platelets in irradiated mice. In addition, ginsan induced the production of a variety of cytokines such as IL-1, IL-6, IL-12, TNF-a and SCF, which are required for a hematopoietic recovery and are closely correlated with the antioxidant defense systems. We demonstrated that the pretreatment with ginsan protected the mice from the lethal effects of ionizing radiation more effectively than given after the irradiation. A dramatic increase of the survival of the ginsan-treated group from LD50/30 7.54 Gy of the PBS-control group to 10.93 Gy was observed. Moreover, the levels of the antioxidant enzymes such as superoxide dismutase (SOD), catalase and gluthathion peroxidase (GPx) were increased 1.5-2 fold in the ginsan treated mice compared to the irradiated mice. In conclusion, our data suggests that the radioprotective action of ginsan in the irradiated mice may be due to not only to the rapid regeneration of hematopoietic cells but also to the modulation of antioxidant defense systems.