Objective High altitude pulmonary edema(HAPE), a life-threatening disease, has no biological markers used for the routine prevention, diagnosis and treatment. The aim of this study was to identify serum proteins differentially expressed in patients with HAPE for discovering essential biomarkers. Methods A complete serum proteomic analysis was performed on 10 HAPE patients and on 10 high altitude and 11 sea level healthy people as control using two-dimensional gel electrophoresis, followed by matrixassisted laser desorption/ionization mass spectrometry and peptide mass fingerprinting. Finally, two most significantly changed proteins were validated by enzyme-linked immunosorbent assay(ELISA). Results Eight protein spots stained with differential intensity, respresenting 5 distinct proteins were identified in patients compared with healthy controls through analysis of these composite gels. Among them, four proteins, namely alpha 1-antitrypsin(α1-AT), Haptoglobin(Hp), apolipoprotein A-I(apoA-1) and Complement C3 increased remarkably, while one protein, apolipoprotein A-IV(apoA-IV) decreased significantly. The variation of α1-AT and Haptoglobin, as detected by ELISA, was consistent with the results from proteomic analysis. Conclusions It is well known that Hp, α1-AT and complement C3 are associated with inflammation and apoA-1 and apoA-IV play important roles in lipid absorption, transport and metabolism. Therefore, the significant expression changes of Hp, α1-AT and complement C3 and apoA-1 and apoA-IV between HAPE patients and their corresponding healthy controls highlight the role of inflammatory response system and lipid metabolism system in the pathophysiology of HAPE. Objective High this is study of catheters differentially expressed in patients with HAPE for discovering essential biomarkers. Methods A complete serum proteomic analysis was performed on 10 HAPE patients and on 10 high altitude and 11 sea level healthy people as control using two-dimensional gel electrophoresis, followed by matrixassisted laser desorption / ionization mass spectrometry and peptide mass fingerprinting. Finally, two most Signific changed proteins were validated by enzyme-linked immunosorbent assay (ELISA). Results Eight protein spots stained with differential intensity, respresenting 5 distinct proteins were identified in patients compared with healthy controls through analysis of these composite gels. Among them, four proteins alpha 1-antitrypsin (α1-AT), Haptoglobin (Hp), apolipoprotein AI (a The variation of α1-AT and Haptoglobin, as detected by ELISA, was consistent with the results from proteomic analysis. Conclusions (pA-1) and Complement C3 increased remarkably, while one protein, apolipoprotein A-IV It is well known that Hp, α1-AT and complement C3 are associated with inflammation and apoA-1 and apoA-IV play important roles in lipid absorption, transport and metabolism. Thus, the significant expression changes of Hp, α1-AT and complement C3 and apoA-1 and apoA-IV between HAPE patients and their corresponding healthy controls highlight the role of inflammatory response system and lipid metabolism system in the pathophysiology of HAPE.