Adiponectin is an adipocyte-derived collectin that acts on a wide-range of tissues including liver, brain, heart, and vascular endothelium. To date, little is known about the actions of adiponectin in the lung. Herein, we demonstrate that adiponectin is present in lung lining fluid and that adiponectin deficiency leads to increases in pro-inflammatory mediators, and an emphysema-like phenotype in the mouse lung. Alveolar macrophages from adiponectin deficient mice spontaneously display increased production of tumor necrosis factor- (TNF-) and matrix metalloproteinase (MMP12) activity. Consistent with these observations, we found that pre-treatment of alveolar macrophages with adiponectin leads to TNF- and MMP12 suppression. Together, our findings show that adiponectin leads to macrophage suppression in the lung, and suggest that adiponectin-deficient states may contribute to the pathogenesis of inflammatory lung conditions such as emphysema.