Cancer is one of most frequent causes of death worldwide. Radiotherapy is an effective method for the treatment of malignant diseases, including cancers of the head-and-neck area. Despite optimal dose distribution and application are normal tissues unavoidably exposed to partially significant doses. The most frequent early side effect in head-and-neck radiotherapy is radiation-induced oral mucositis, characterized by ulcerative lesions of the oral mucosa. Therapeutic irradiation results in local changes of perfusion. This could lead to an impairment of local oxygen supply (hypoxia). Dermatan sulphate showed significant mucositis reducing effects in functional preclinical studies. These might be based on an amelioration of radiation-induced local hypoxia by the anticoagulative activity of dermatan sulphate. In the present study, hypoxia was determined by an intrinsic marker – Glucose Transporter 1 (GLUT1) - and an extrinsic marker - Pimonidazole (PIMO) - respectively. During the first week of irradiation the relative number of GLUT1 membrane-positive cells remained within the control range. Values increased drastically in the second week to 400 % of the control value at the end of the observation period. From day 10, dermatan sulphate substantially reduced the relative number of GLUT1 positive cells as well as the GLUT1 staining intensity. PIMO staining did not correlate with the results of GLUT1 staining; PIMO hence might not be suitable to investigate radiation-induced hypoxia in murine oral mucosa. The by GLUT1 detected effect of dermatan sulphate could potentially contribute to the mucoprotective activity of dermatan sulphate. The underlying mechanisms, however, are unknown and require further investigations.