Abstract: Surfactant protein D (SP-D) is a 43-kDa member of the collectin family of collagenous lectin domain-containing proteins that is expressed in epithelial cells of the lung. The SP-D gene was targeted by homologous recombination in embryonic stem cells that were used to produce SP-D (−/−) mice. The SP-D (−/−) deficiency caused inflammation, increased oxidant production by isolated alveolar macrophages, abnormal surfactant structure and levels, and decreased SP-A expression. Therefore, disclosed is the SP-D (−/−) mouse as an excellent model for emphysema. Also included are models for testing emphysema therapies in the mouse model, methods for using SP-D protein or DNA as a treatment for emphysema and pulmonary infections, and diagnosis.