Emphysema is a pulmonary disease characterized by alveolar wall destruction, resulting in enlargement of gas exchange spaces without fibrosis, This condition is a part of chronic obstructive pulmonary disease (COPD), which causes 3.5% of deaths worldwide [Anonymous (1990) World Health Stat Q. Special, 1-51] and contributes greatly to the global burden of disease [Murray, C, J, & Lopez, A. D. (1996) Science 274, 740-743]. Alveolar regeneration has been shown in animal models and could have potential for clinical treatment of early-stage emphysema, However, current techniques for detection of emphysema are not sensitive at the initial stages. Early-stage human panacinar emphysema is modeled in elastase-treated animals. Here, we provide an in vivo imaging method for differentiating normal and emphysematous rat lungs by measuring the apparent diffusion coefficient (ADC) of hyperpolarized He-3 by using magnetic resonance imaging. These data show that the ADC is significantly larger in elastase-treated rats, indicating alveolar expansion. Whereas these rats were clinically asymptomatic, conventional histology confirmed presence of injury. Our results indicate that measurement of the hyperpolarized He-3 ADC can be a valuable research tool and has potential application in the clinical setting.