The current study was to test an experimental model of actinic lesions in the distal intestine of rats and to determine the possible protective effect of hyperbaric oxygen therapy (HBO2) in radio-induced lesions when concomitantly applied with ionizing radiation. Twenty-four Wistar rats were divided into four groups: G1 (control group); G2 (animals irradiated); G3 (animals irradiated plus HBO2); G4 (only HBO2). The animals were evaluated for 28 days after the end of treatment and then euthanized. The distal intestine was resected for macroscopic and microscopic evaluation and immunohistochemistry. The animals in the G3 group lost weight during the treatment; all of the animals in the G2 group presented macroscopic mucosal lesions up until 28 days; the animals in the other three groups did not present macroscopic lesions. Microscopic mucosal lesions were observed in the specimens of the animals treated with ionizing radiation; in the animals from the G3 and G4 groups the lesions were less intense. For the immunohistochemical analysis, we observed the specimens taken from G3 group animals had more CD34+ cells. The experimental model proved to be useful in causing radio-induced lesions, and concomitantly applied HBO2 is capable of reducing late actinic lesions.