Micro-computed tomography (microCT) is being increasingly used to examine small animal models of pulmonary injury. The authors have developed a microCT technique suitable for the determination of pulmonary compliance in injured mice. Lung volumes in normal mice were radiographically determined at end-inspiration and end-expiration and pulmonary compliance was calculated at 2 time points 2 weeks apart, whereas a second group of mice were given bleomycin and imaged 3 weeks following drug administration. Compliance measurements were validated using a commercially available ventilator system. MicroCT pulmonary compliance measurements are suitable for longitudinal measurements, and correlate with physiologic measurements of pulmonary compliance.