Background: Adrenomedullin (AM) and its receptor, receptor activity-modifying protein (RAMP) 2 have pleiotropic regulatory functions in normal tissue and cancer tissue. AM is produced and secreted both numerous stromal cells and tumor cells. This study aims to investigate a possible role of AM and RAMP2 in the radiation exposure in the normal lung tissue. Materials and Methods: Four groups with 6 male adult Swiss Albino mice per group were investigated. The mice were subjected to a 500 cGy single-dose radiation exposure in the total body radiation device and lung tissues were collected. 1, 2, and 7 days after radiation exposure, with 1 reference group which was not exposed to radiation. Results: The general histology and the immunohistochemistry of the tissue samples prepared with anti- AM, anti–RAMP2, and monoclonal antibodies were investigated, yielding a statistically significant increase for AM on day 3 and for RAMP2 on day 1 after radiation exposure. Conclusion: The observed increase of AM and RAMP2 concentrations in the normal tissue matrix after radiation exposure may play a role in the side effects of radiotherapy.