Radiotherapy is one of the main treatments against cancers. However, it presents a risk of adverse effects for the normal tissues surrounding the tumors. The vascular network and especially the endothelium are considered as main targets to limit normal tissue damages and prevent side effects of radiotherapy. Activated endothelial cells are involved in the chronic recruitment of thrombocytes and leukocytes, resulting in tissue complications. On the other hand, in inflammatory diseases, the glycans expressed on the surface of endothelial cells are modified and lead to immune cells recruitment. In this work, we sought to evaluate changes in endothelial glycome in a context of exposure to high dose of radiation, and studied the functional consequences on the recruitment of leukocytes. In vitro, the characterization of the glycome was performed on a primary endothelial cell model (HUVEC). Our results provide the first evidences of an endothelial modification of the glycome after exposure to ionizing radiation. We report an overexpression of high mannose N-glycans, O-glycans and syalilated motifs. At the same time, endothelial glycocalyx appeared to be damaged by exposure to radiation. Next, we evaluated these radiation-induced modifications of endothelial glycans on monocyte adhesion. We show that the radiation induced adhesion was mediated by overexpression of high mannose N-glycans. We also investigated changes in glycome in an irradiated mouse model of enteropathy and in resections of patients treated with radiotherapy. In mice, a transcriptomic study suggests changes in glycans following radiation exposure. Collectively, these findings on glycome changes provide a new perspective of the continuum of events leading to normal tissue complications. In the future, the study of the glycome should open new therapeutics opportunities for better management of tissue damages induced by radiation.