Radiation can induce senescence in many organs and tissues; however, it is still unclear how radiation stimulates senescence in mouse small intestine. In this study, we use the bone marrow transplantation mouse model to explore the late effects of total body irradiation on small intestine. Our results showed that almost all of the body hairs of the irradiated mice were white (which is an indication of aging) 10 months after the exposure to radiation. Furthermore, compared with the age-matched control mice, there were more SA-β-galactosidase (SA-β-gal)–positive cells and an upregulation of p16 and p21 in 8 Gy–irradiated mice intestinal crypts, indicating that radiation induced senescence in the small intestine. Intestinal bacterial flora profile analysis showed that the diversity of the intestinal bacterial flora decreased in irradiated mice; in addition it showed that the principal components of the irradiated and control mice differed: there was increased abundance of Bacteroidia and a decreased abundance of Clostridia in irradiated mice. To explore the underlying mechanism, an RNA-sequence was executed; the results suggested that pancreatic secretion, and the digestion and absorption of proteins, carbohydrates, fats and vitamins were damaged in irradiated mice, which may be responsible for the body weight loss observed in irradiated mice. In summary, our study suggested that total body irradiation may induce senescence in the small intestine and damage the health status of the irradiated mice.