Objective To investigate the effects of irradiation on the osteogenesis potential of bone marrow mesenchymal stem cells (BMMSCs) and EM>in vivo/EM> bone system. Methods At 28 days after 4Gy total body irradiation (TBI), BMMSCs were isolated from irradiated or normal male C57BL/6 mice and cultured. Their osteogenesis potential was evaluated by alkaline phosphatase (ALP) and Von Kossa staining after 1 and 3 weeks osteogenic differentiation EM>in vitro/EM> respectively. Bone histomorphometric analysis including hematoxylin and eosin (HE) and toluidine blue staining, bone mineral density (BMD) measurment were performed to detect the changes in bone systemEM>in vivo/EM>. Results Significant impairment of osteogenic differentiation of BMMSCs at 28 days post irradiation was observed in both ALP and Von Kossa staining with less ALPpositive cells after 1 week of culture in osteogenic culture and a calciumless mineralized matrix in the induction dish after 3 weeks of induction. Meanwhile, the trabecular structure was gradually fragmented after irradiation and at 15 weeks after TBI, the irradiated mice had decreased total body bone mineral density. Conclusion Irradiation resulted in decrease in osteogenesis potential of BMMSCs accompanied by bone injury, and the damage in BMMSCs may be, at the stem cell level, invo