In this study we investigated the effect of repeated low-dose radiation exposure (75 mGy X ray) on skin wound healing in a rat model of diabetes. A skin wound was made on the backs of diabetic and age-matched control rats 60 days after diabetes was induced by a single injection of streptozotocin. Rats with skin wounds were immediately treated with whole-body radiation daily for 5, 10 or 15 days with a 2-day break every 5 days. Wound size was estimated 5, 10 and 15 days after wound formation. Repeated exposure of diabetic rats to low-dose radiation significantly accelerated skin wound healing compared to the nonirradiated diabetic group. Furthermore, low-dose radiation-induced improvement in healing was associated with increases in bone marrow and circulating CD31(+)/CD34(+) stem cells, vessel regeneration and cell proliferation in the wound tissue, and matrix metalloproteinase 2 and 9 expression. Therefore, we conclude that the acceleration of wound healing in diabetic rats by repeated exposure to low-dose radiation is associated with stimulation of bone marrow stem cell proliferation and peripheral mobilization.