Post-natal lung maturation generates a large number of small alveoli, with concomitant thinning of alveolar septal walls, generating a large gas exchange surface area but minimizing the distance traversed by the gases. This demand for a large and thin gas exchange surface area is not met in disorders of lung development, such as bronchopulmonary dysplasia (BPD), histopathologically characterized by fewer, larger alveoli; and thickened alveolar septal walls. Diseases such as BPD are often modeled in the laboratory mouse to better understand disease pathogenesis, or develop new interventional approaches. To date, there are no reports of stereology-based longitudinal studies on post-natal mouse lung development that report dynamic changes in alveoli number or alveolar septal wall thickness during lung maturation. To this end, changes in lung structure were quantified over the first 22 months of post natal life of C57BL/6J mice. Alveolar density peaked at post-natal day (P)39, and remained unchanged at nine months (P274), but was reduced by 22 months (P669). Alveoli continued to be generated, initially at an accelerated rate between P5 and P14, and at a slower rate thereafter. Between P274 and P669, loss of alveoli was noted, without any reduction in lung volume. A progressive thinning of the alveolar septal wall was noted between P5 and P28. Pronounced sex differences were observed in alveoli number in adult, but not juvenile mice, comparing male and female mouse lungs, which were attributed exclusively to the larger volume of male mouse lungs.