The radioprotective activity of Nigella sativa extract (NSE) was ascertained by administering mice orally with 25,50, 100, 150, 200, 400 or 500 mg/kg b. wt. of NSE, once daily for five consecutive days prior to 10 Gy γ-irradiation. One hour after the last administration of NSE on fifth day, the animals were whole body exposed to 10 Gy radiation. The exposure of animals to 10 Gy irradiation resulted in the death of all irradiated animals within 16 days postirradiation, whereas administration of mice with different doses of NSE reduced the radiation-induced mortality and increased the animal survival significantly (p<0.05). The maximum number of survivors (60%) was observed in the group of animals treated with 150 mg/kg NSE. A further increase in the NSE dose up to 500 mg/kg did not significantly elevate the animal survival when compared to 150 mg/kg. Since maximum number of survivors was observed with 150 mg/kg of NSE, it was considered as an optimum dose for radioprotection and further experiments were performed using this dose. In another set of experiments the animals were administered with 150 mg/kg b. wt. of NSE orally once daily for five consecutive days before exposure to 7, 8, 9, 10 or 11 Gy γ-radiation, where the animals were monitored daily up to thirty days post-irradiation for the development of symptoms of radiation sickness and mortality. Treatment of mice with NSE before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the double distilled water (DDW) treated irradiated controls. The LD 50/30 was found to be 8 Gy for DDW + irradiation group, whereas the NSE treatment increased LD 50/30 up to 9.6 Gy with a dose reduction factor (DRF) of 1.2. The in vitro studies in cell free system revealed that NSE inhibited the generation of various free radicals including 2,2-diphenyl-2-picryl hydrazyl (DPPH), 3-ethyl benzothiazoline-6sulphonic acid (ABTS •+ ), hydroxyl (OH • ) and superoxide (O2 •-) in a concentration dependent manner. The radioprotective effect of NSE may be due to free radical scavenging and increased antioxidant status.