Background: Cigarette smoking is the major risk factor for several forms of lung disease including COPD. Up to date, no effective therapies to reverse or retard the course of the disease are available. Thus, proteomic analysis of COPD may be important for understanding the pathobiology of COPD at the protein levels. Our study suggested that differentially expressed proteins in human plasma were evaluated for development of COPD. Objective: To identify plasma biomarkers in COPD and to compare protein profiles in plasma between stable and exacerbation with COPD. Methods: We examined the plasma of nomal control (n=8) and COPD stable (n=8) and exacerbation (n=8) using 2-DE, respectively. The differentially expressed protein spots were identified by MALDI-TOF/TOF. ELISA were performed for identification and quantitative measurement of RARα in plasma from nomal control (n=37) and COPD stable (n=35) and exacerbation (n=21). Results: 17 proteins were identified to be differentially expressed in plasma between COPD stable and COPD exacerbation by MALDI-TOF/TOF. We found that 10 proteins were increased in plasma of stable, while 7 proteins were lower in stable than exacerbation. One of these proteins was associated with RARα protein. The result of the subjects with COPD exacerbation had significantly higher plasma levels of RARα than COPD stable and normal control subjects. Conclusion: The proteomic analysis of plasma indicates that alteration of various proteins may be associated with COPD development.