The effective treatments of radiation-induced intestinal injury are currently unavailable. Developing new treatments for radiation-induced intestinal injury is thus important. The present study investigated whether transplantation of mesenchymal stem cells (MSCs) is able to prevent radiation-induced intestinal injury. Intestines of female nude mice (ICR nu/nu) were irradiated at a single dose of 30 Gy. Transplantation of male MSCs (C57BL/6) was then immediately performed into the walls of irradiated intestine by direct injection for the irradiation + MSCs group. Mice were weighed daily and survival was recorded for 13 days after irradiation. From 13 to 27 days after irradiation, intestines of mice were obtained in order to assay histological changes by staining with hematoxylin-eosin and Masson trichrome. Mean body weight of the irradiation + MSC group was significantly higher than that of the irradiation-only group from 8 days after irradiation. In addition, survival rates were significantly higher in the irradiation + MSC group than for the irradiation-only group from 5 days after irradiation. Histological observation revealed that intestines of irradiation + MSC-transplanted mice were thick in the submucosal and muscle layers, and had almost fully recovered from radiation-induced intestinal injury at day 27. Specifically, ulcerated areas in the intestines of the irradiation + MSC-transplanted mice were smaller by 13 days after irradiation and were fewer in numbers at 27 days when compared with the irradiation-only group. Our results suggest that transplanted MSCs may play an important role in preventing radiation-induced injury and may offer a novel method to treat radiation-induced intestinal injury.