Objective To investigate the antioxidative protective effects of Eupolyphaga sinensis Walker (ESW) polypeptides on carbon tetrachloride (CCl4 )-induced chronic liver injury in mice. Methods Mice were randomly divided into the normal, model, ESW peptides ( 50, 100, 200 mg / kg) or positive drug groups. Mice in control group were intraperitoneally administred physiological salt solution. Mice in the ESW peptides group were intraperitoneally administered different doses of ESW peptides, and the positive drug group was intraperitoneally administered 100 mg / kg silymarin daily for 6 consecutive weeks. All mice except those in the normal group were intraperitoneally injected with 0. 1% CCl4 peanut oil solution (10 mL/ kg) twice weekly for 6 consecutive weeks. Twenty-four hours after the final administration, the mice were weighed and sacrificed, and their liver tissues were removed, processed and stained with hematoxylin and eosin to evaluate the changes in liver histology. Liver function enzymes (AST and ALT), antioxidant enzymes and peroxide (MDA) were detected via spectrophotometry. Inflammatory factors, apoptotic factors and fibrosis factor gene expression were determined via quantitative PCR. Enzyme-linked immunosorbent assay was used to assay inflammatory factor protein levels. Results No microscopic abnormalities were found in the liver cells of the normal group. In the model group, the hepatocytes showed hyperemia, necrosis and fibrosis, and the hepatic lobules had disappeared. The morphological structures of the hepatocytes in the ESW peptides group were damaged, but increasing the ESW peptide dose significantly lessened the degree of the injury, and the liver and spleen indices of these mice were significantly lower than those of the model group. Compared with the model group, the serum Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) enzyme activities and the MDA content in the livers of the mice in the ESW peptides group were significantly decreased. Additionally, the antioxidant enzyme ( SOD, CAT, GSH-Px ) activities were significantly improved, the inflammatory factor (IL-6, TNF-α, iNOS) protein and gene expression levels were significantly decreased, and the pro- apoptotic factor (Bax, Bcl-2, Caspase-3) and fibrosis factor (α-SMA, TGF-β) gene levels were significantly decreased and positively correlated with the ESW polypeptide dose. Conclusions ESW peptides attenuates CCl4 -induced chronic liver injury in mice, and these protective effects may be closely related to the peptides’ antioxidant effects.