To investigate the late effects of thoracic region irradiation (TRI) on mouse body weight. Female C57BL/6 mice were divided into nonirradiated, 5 Gy total body irradiation, 9 Gy sub-total body irradiation, and 12.5 Gy thoracic region irradiation (TRI) groups. Changes in mouse weight were monitored every other week at similar time points for 12 months. The anatomical characteristics of abdominal visceral fat distribution were recorded, and mitochondrial DNA copy number in the hearts and livers and lipid metabolic signaling in the liver were analyzed. Data were analyzed by one-way analysis of variance and a student's t-test. TRI led to a significant increase (p < .001) in body weight that was dependent on time and individuals [42.1% of mice were overweight (50% increase in body weight) 4 months post-TRI and 100% of mice were overweight at 10 months post-TRI]. Gross anatomical features of abdominal visceral fat distribution and storage in radiation-induced overweight/severely overweight mice were similar to those of high fat diet-induced overweight/severely overweight mice. The mitochondrial genome of heart and liver tissues from overweight/severely overweight mice had significantly (p < .05) decreased functional mitochondrial DNA copy number (ratios decreased from 1 to 0.71 or 0.49, respectively) and significantly (p < .05) increased mitochondrial DNA mutations (ratios increased from 1 to 3.21 or 1.83, respectively). CPT1 and IRS2 lipid metabolic signaling was significantly (p < .05-.01) decreased for both mRNA (fold decrease from 1 to 0.60 or 0.55, respectively) and protein (fold decrease from 1 to 0.62 or 0.19, respectively). TRI can cause mice to gain weight. These findings indicate that TRI can result in lipid metabolic abnormalities and provide a model to study the factors that result in these abnormalities.