To explore the differential proteome pattern in mouse fibrosis liver in comparison to wild type. Mice were fed with carbon tetrachloride or olive oil vehicle for 15 weeks. Mouse livers from both groups were collected and submitted to MS platform for proteome screening. GO (Gene Ontology) biological process and KEGG (Kyoto Enyoolpedia of Genes and Genomes) pathway enrichment analysis were used to analyze differentially expressed proteins. As the results, we identified 17 382 and 20 486 unique peptides in control and carbon tetrachloride-induced groups, respectively. A total of 4 991 proteins (at least 1 unique peptide matched) were identified, of which 2 135 were differentially expressed (> or = 2 fold). In fibrosis mouse liver 1 264 proteins were up regulated and 871 proteins were down regulated. Proteins associated with DNA replication, cell cycle, ECM-receptor interaction, and splicesome were significantly increased in carbon tetrachloride-induced group. Proteins associated with small molecule metabolic process, protein transport, organonitrogen compound metabolic process, and tetrapyrrole biosynthetic processes were down regulated in carbon tetrachloride-induced mouse liver fibrosis tissue. Bioinformatics findings showed that fibrosis was closely related to the regulation of VEGF and T cell receptor signaling pathway, and further suggested that liver fibrosis was a complex signal transduction process that many biological processes such as liver metabolism, inflammation, and immune response are involved. Based this study, we can envision that protection of protein metabolism in liver parenchymal cells and blocking of inflammatory signaling transduction may be beneficial for liver fibrosis therapy.