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Aim Liver fibrosis is a consequence of chronic liver disease which can progress into liver cirrhosis even hepatocarcinoma.FuzhengHuayu (FZHY), a Chinese herbal formula, had been reported to have the effect of antifibrosis.This study aims to investigate the effective targets and the mechanisms of FZHY on liver fibrosis.Methods The liver tissue samples of normal group, model group and FZHYtreated group were examined by microarray and iTRAQ.Profiles of differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in CCl4induced liver fibrosis model in rat were analyzed.GO and Pathway were analyzed by DAVID, and proteinprotein interaction (PPI) was analyzed by STRING and cytoscape.The targets of FZHY compounds were predicted by TCMSP.Results The results showed that 255 genes (fold change > 1.5, P < 0.05) and 507 proteins (fold change ≥1.2 ,P <0.05) were differentially expressed between FZHY group and model group.The highthroughput data of transcriptomics and proteomics was analyzed synthetically.DAVID function annotation analysis showed that these DEGS and DEPs both enriched in 15 GO terms, among drug metabolic process, response to extracellnlar stimulus,response to vitamin, arachidonic acid metabolic process, response to wounding and oxidation reduction may involve in liver fibrosis.KEGG pathway analysis showed that these DEGS and DEPs both enriched in 9 pathways, among arachidonic acid metabolism, retinol metabolism, metabolism of xenobiotics by cytochrome P450 and drug metabolism may be related to liver fibrosis.PPI analysis found that 10 overlapped core genes and proteins, among,Ugt2a3, Cyp2b1 and Cyp3a18 were of higher degree, which are all enriched in retinol metabolism.Interestedly,Cyp2b1 and Cyp3a18 were also predicted with TCMSP as the targets of FZHY compounds.Conclusion The resuits indicated that the effective mechanism of FZHY against liver fibrosis is involved in the regulation of multiple targets and multiple pathways, among, retinol metabolism pathway by targeting Ugt2a3, Cyp2b1 and Cyp3a18 may play an important role in the treatment of liver fibrosis.