Methods of preventing, ameliorating and/or treating radiation induced gastrointestinal tract injury comprising the administration of a therapeutically effective amount of Mesna to a patient are provided. Methods for preventing, treating and/or ameliorating gastrointestinal tract injury induced by radiation therapy, alone or in combination with other therapies for diseases or conditions such as gastrointestinal malignancies, urogenital malignancies, gynecologic malignancies, and osteogenic and other sarcomatous malignancies in which pelvic structures are involved.