Background: Mitochondria are now considered as one major target for many therapeutic approaches. Oxidative stress has been a particular fulcrum of interest since mitochondrial oxidative damage has been recognized as being involved in many diseases and in the aging process itself. Also, disrupted mitochondrial metabolism may be one of the critical elements leading to cancer, diabetes, ageassociated and neurodegenerative disorders. In addition, the link between sirtuin activity and mitochondrial biology has recently emerged as an important field. Although SIRT1 has benn reported to play an important role in the pathogenesis of bronchial asthma, there are little experimental data on the relationship between this cytoplasmic and nuclear sutuin, SIRT1 and mitochondrial ROS in respiratory disorders. Methods: Using LPS-instilled mice and epithelial cells, we evaluated the role of mitochondrial ROS and SIRT1 in the pathogenesis of LPS-induced lung injury. Results: In this study, we have found that the SIRT1 expression was significantly increased in LPS-induced lung infiammation with showing the increased generation of total cellular ROS and mitochondrial ROS, increased in plasma exudation, the increasd numbers of airway infiammatory cells in BAL fiuids, the histologic changes in lung tissues, and the increase in the levels of infiammatory cytokines. These findings were attenuated by the administration of mitochondrial ROS inhibitor, NexroX-5. Moreover, the administration of the SIRI1 inhibitor, sirtinol significantly reduced the LPS-induced lung infiammation, pathologic damage, and plasma exudation. Conclusions: These findings suggests that the interaction between mitochondrial ROS and SIRT1 contributes to the pathogenesis of LPS-induced lung infiammation cooperatively, providing a new target for the therapeutic approach to various lung infiammatpry disorders including infectious disease.