Highly pathogenic porcine reproductive and respiratory syndrome (PRRS) was large-scalely outbreaked in China and Vietnam in 2006 and 2007.To better understand host immune response to both highly virulent Chinese-type PRRSV (H-PRRSV) and normal North American-type PRRSV strains (N-PRRSV),we firstly established an animal model infected with either H-PRRSV or N-PRRSV.Then differential proteomes of porcine lungs infected with H-PRRSV,N-PRRSV and uninfected negative control were analyzed at different time points using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and mass spectrometry identification.45 differentially expressed proteins (DEPs) were identified.These proteins were mostly related to cytoskeleton,stress response and oxidation reduction or metabolism.In the protein interaction network constructed based on DEPs from lungs H-PRRSV infected,HSPA8,ARHGAP29 and NDUFS1 belonged to the most central proteins,whereas DDAH2,HSPB1 and FLNA corresponded to the most central proteins in those of N-PRRSV infected,suggesting differential host immune response.Our study is the first attempt to compare the complex picture of pulmonary protein expression during H-PRRSV and N-PRRSV infection under the in vivo environment using 2D-DIGE technology and bioinformatics tools,prorides large scale valuable information for better understanding host immune response to these two PRRSV strains and potential molecular pathogenesis.