To investigate septic lung injuries and the possible relief from injury by carbon monoxide (CO), rats were intraperitoneally (i.p.) administered water or the water-soluble CO-releasing molecule CORM (30 mg/kg body weight), followed by the successive administration of PBS or lipopolysaccharide (LPS, 15 mg/kg body weight, 6 h). The results in four experimental groups (control, LPS, LPS + CORM, CORM, n = 3 or 4 in each groups) were examined. Histological examination revealed the intravascular aggregation of erythrocytes in the lungs of the LPS group, and serological analysis showed a significant increase in D-dimer in the LPS group. Both the aggregation and D-dimer increase were ameliorated in the LPS + CORM group, suggesting that LPS-induced DIC in the lung is ameliorated by CORM. Proteomic as well as immunoblot analyses revealed that the levels of annexin A(2) (AnxA(2)) were significantly decreased in the LPS group, but were at control levels in the LPS + CORM group. Concordant with the levels of AnxA(2), the levels of both LC3 and collagen VI (COL VI) were decreased in the LPS group but not in the LPS + CORM group. Given the established roles of AnxA(2) in fibrinolysis as well as intracellular vesicle trafficking, AnxA(2) down-regulation should play an important role in the pathogenesis of septic lung injuries. (C) 2017 Elsevier Inc. All rights reserved.