Elucidation of the mechanisms of liver fibrogenesis is important to treat liver fibrosis.In this study,we established rat models of liver fibrosis with stages from 0–1,2,and 3–4 to 4 at 2,4,6,and 8 weeks,respectively,by injection of pig serum.Liver fibrogenesis was detected by Masson’s trichrome staining.Rat non-parenchymal cells(NPCs)were enriched 4-fold by Percoll density gradient centrifugation.Protein extracts from NPCs were prepared at 4 and 8 weeks,separated by two-dimensional electrophoresis,and then stained with Coomassie Blue G-250.At 4 weeks,we identified 18 non-redundant differentially expressed proteins of which protein disulfide-isomerase associated protein 3(PDIA3)and NDUV showed consistent expression at protein and mRNA levels from 4 to 8 weeks.PDIA3 was found to be down-regulated by Western blotting in the rat model and immunohistochemically in human liver.Our results revealed important aspects of the pathogenesis/progression of liver fibrosis and demonstrated important changes in protein expression levels of NPCs at various stages of liver fibrosis.