The hormetic effects of exercise training have previously been shown to enhance cellular protection against oxidative stress. Therefore, adaptations to exercise training may attenuate the harmful effects of radiation induced by oxidative stress. Flow cytometric analysis of genotoxicity (γH2AX foci and micronucleated reticulocytes (MN-RET)) and cytotoxicity (apoptosis and percentage of reticulocytes) were conducted on bone marrow cells isolated from acutely exercised (Acute EX), exercise-trained (EX), and sedentary (SED) mice following 1 and 2 Gy radiation challenges in vitro. Acute EX increased the percentage of cells with activated caspase-3 and -7 (32%, p < 0.001) and γH2AX foci formation in response to 2 Gy radiation challenge (10%, p < 0.05). Exercise training significantly attenuated γH2AX foci formation and MN-RET production in response to 1 Gy radiation challenge (18%, p < 0.05 and 22%, p < 0.05, respectively). Exercise training also significantly reduced basal percentages of cells with activated caspase-3 and -7 and in response to radiation in bone marrow cells (11%, p < 0.05). These results suggest that oxidative stress caused by acute exercise induces an adaptive response responsible for the radioprotective effects of exercise training.