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To identify characteristics of lung fibrosis in a mouse model after radiotherapy (RT) using thin-section computed tomography (CT), histology and clinical parameters.Using a multislice CT-scanner, follow-up chest CT scans of 10 out of 72 included mice (C57BL/6J, 36 control mice, 36 mice (20Gy)) were performed every 2 weeks until week 26 after RT. Hounsfield units (HU) and cardiothoracic ratio (CTR) were measured, and a multireader analysis on characteristic lung changes was performed and correlated with histology and clinical parameters.From weeks 4 to 8 after RT changes in histology (leukocyte count, extraalveolar edema, P < 0.01) and from week 12 changes in CT were detected (increase in HU, intralobular opacity and fibrotic strandings, P < 0.05). From week 14 clinical manifestations occurred (loss of weight, mobility, breathing, increased mortality, P < 0.01). CTR showed no significant changes. Three readers showed excellent interobserver agreement (κ >0.84).Thin-section CT in a mouse model is capable of detecting the development of lung fibrosis after RT prior to the onset of clinical deterioration.