Aim: To evaluate dynamic tissue changes after airway stenting (AS) with a newly designed metal brachytherapy stent (BS) loaded with radioactive 125I seeds in normal rabbits. Methods: Forty-five normal New Zealand white rabbits were divided into 3 groups (group A: stent without seeds; group B: stent with 0.4 mCi active seeds; group C: stent with 0.8 mCi active seeds) and underwent AS under C-arm guidance. Then, five rabbits were killed from each group at 2, 4, and 8 weeks for further examination. Laboratory tests (including routine blood tests, liver function, kidney function, and electrolytes), gross observations, and tissue changes of Masson/hematoxylin–eosin staining, plus immunohistochemistry of α-SMA, NOX4, and TGF-β were performed at each time point. Results: All animals underwent AS successfully without procedure-related death, but one animal died at 6 weeks due to severe pulmonary infection in group C. Apart from a transient increase in white blood cells (P < 0.05) and a gradual increase in ROS levels (P < 0.05), other blood test items showed no significant changes (P > 0.05). The brachytherapy injury score increased with irradiation dose accumulation (P < 0.05), but tissue hyperplasia at the stent end in group C was less severe than that in groups A and B (P < 0.05). Airway lateral fibrosis was observed in all groups by histopathologic analysis; however, fibrosis in group C was more severe than that in groups A and B (P < 0.05). Conclusion: The brachytherapy injury score increased with irradiation dose accumulation, while granulation tissue hyperplasia at the stent end was inhibited by 125I brachytherapy within 8 weeks. [ABSTRACT FROM AUTHOR]