Abstract Aim: To investigate the role of endothelial cell damage in radiation‐induced lung injury. Methods: A total of 60 male Sprague–Dawley rats were irradiated to the right hemithorax with a single dose of 0, 7.0 or 14.4 Gy. Serial studies were performed before and at 1, 7, 30 and 90 days after radiation, respectively. Pathological studies were carried out to detect changes in the lung after irradiation. Western blot studies were conducted to detect the expression of CD34 and of CD105 and vascular endothelial growth factor (VEGF). Results: Compared to controls, the irradiated rat lung showed a dose‐dependent and time‐dependent decrease in the expression of CD34. The level of CD105 was significantly reduced by irradiation except at 90 days after radiation. The expression of VEGF increased 1 day after radiation, and then decreased from day 30 onwards, to be lower than the control group at 90 days. Pulmonary fibrosis was observed at 90 days after 14.4 Gy exposure; however, most of these phenomena were not observed in the 7.0 Gy group. Conclusion: These results support the notion that endothelial cells play an important role in radiation‐induced lung injury, and may be critical to breakdown of the blood–alveolus barrier and microcirculation dysfunction related to radiation‐induced inflammation and fibrosis.