Pulmonary emphysema is one of the distinct pathological forms of chronic obstructive pulmonary disease (COPD) that is accompanied by gradual elimination of alveolar tissue, causing reductions in lung recoil and leading to difficulty in breathing. As there is no cure for emphysema, animal models are often used to better understand the pathogenesis and progression of the disease. One widely used animal model of emphysema is the elastase treatment. In this chapter, we describe two methods of elastase-induced emphysema in mice. The first is a single-dose treatment, whereby elastase is introduced oropharengeally into the lung and the structure and/or function of the lungs are studied between 2 days and 4 weeks following the treatment. The second method consists of exposing mice repeatedly (four times) to elastase intratracheally and observing the effects of the treatment 1–4 weeks following the last administration of the enzyme. Both protocols are described in detail, and examples of lung structure and function of the emphysematous mouse lung are provided.