In case of high-dose radiation exposure, mechanisms controlling late visceral organ damage are still not completely understood and may involve the central nervous system. To investigate the influence of cranial/brain irradiation on late visceral organ damage in case of high-dose exposure, Wistar rats were irradiated at 12 Gy, with either the head and fore limbs or the two hind limbs protected behind a lead wall (head- and hind limbs-protected respectively), which allows long-term survival thanks to bone marrow protection. Although hind limbs- and head-protected irradiated rats exhibited similar hematopoietic and spleen reconstitution, a late body weight loss was observed in hind limbs-protected rats only. Histological analysis performed at this time revealed that late damages to liver, kidney and ileum were attenuated in rats with head exposed when compared to animals whose head was protected. Plasma measurements of inflammation biomarkers (haptoglobin and the chemokine CXCL1) suggest that the attenuated organ damage in hind limbs-protected rats may be in part related to reduced acute and chronic inflammation. Altogether our results demonstrate the influence of cranial/brain exposure in the onset of organ damage.