Ultrashort echo time (550 ms) MR imaging was implemented to track the emphysema development in mice lung challenged with elastase. Two parameters, namely, signal intensity and T 2 *, were used to monitor the disease evolution. Nine mice were imaged before and at 24 h as well as at 3 and 8 weeks after elastase instillation. Five mice instilled with saline served as controls. At week 8, the mean normalized signal intensity 6 SD was 0.89 6 0.20 for healthy controls and 0.64 6 0.10 for animals with emphysema. Similarly, a reduced value of T 2 * (1.27 6 0.35 ms vs 0.96 6 0.18 ms) was found in the emphysema group. The mean signal intensity drop and the reduction of T 2 * were prominent at 3 weeks following elastase instillation and stabilized between 3 and 8 weeks. The results indicated an excellent agreement between MR findings and histological morphometry (signal intensity, r 5 20.78, P 5 0.004; T 2 *, r 5 20.78, P 5 0.001). This result shows that proton MRI allows structural changes at alveolar level to be monitored longitudinally. This technique, applied routinely in preclinical trials will represent a valuable tool for assessment of drug therapy efficacy. Magn Reson Med 68:898-904,