Mayumi-Emphysema (ME) mice, which develop spontaneous pulmonary emphysema, were established from wild type C57BL/6J mice. ME mice showed air space enlargement from 2 weeks of age and rapidly developed severe emphysema. The mean linear intercept of the lungs in ME mice was higher than that in control mice at the age of 2 weeks and increased progressively with age in ME mice. However, there was no infiltration of inflammatory cells into the interstitium or alveolar air spaces in the lungs of ME mice. The serum α1-antitrypsin protein level was slightly decreased in ME mice at 4 weeks of age. In ME mice, lung destruction was not associated with an inflammatory reaction, and a slight decrease in serum α1-antitrypsin may be insufficient to induce severe emphysema in ME mice. Hereditary impairment of the normal developmental mechanism for alveoli in the early stage and an abnormal lung structure may induce spontaneous pulmonary emphysema in ME mice.