Objective To investigate the effect of polyinosinic- polycytidylic acid( poly I∶ C) on the activation of natural killer cells( NK cells)in the mouse model of liver injury induced by carbon tetrachloride( CCl4). Methods Eighty C57BL/6 mice were randomly divided into normal control group,poly I∶ C control group,model control group,and poly I∶ C group. The mice in model control group and poly I∶ C group were intraperitoneally injected with 10% CCl4( 2 ml·kg-1·2d-1) to establish the model of liver injury,and the mice in normal control group and poly I∶C control group were intraperitoneally injected with the same dose of olive oil. The mice in poly I∶ C control group and poly I: C group were intraperitoneally injected with poly I∶ C( 1 mg·kg-1·2d-1),and the mice in normal control group and model control group were intraperitoneally injected with the same volume of normal saline. After continuous administration for 4 weeks,serum levels of liver function indices and liver inflammatory factors were observed; HE staining was applied to observe liver inflammation grade; flow cytometry was applied to measure NK cells in the liver,as well as the expression of the activating receptor NKG2 D and inhibitory receptor Ly49 A on NK cells. Analysis of variance was applied for comparison between groups,with least significant difference( LSD) test applied for homogeneity of variance and Dunnett's T3 method applied for heterogeneity of variance. Results After administration of poly I∶ C for 1 week and 4 weeks,there was no obvious liver injury in normal mice. With aggravation of CCl4 poisoning,the model control group,compared with the normal control group,had gradually increased serum levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin( P < 0. 01) and upregulated levels of intrahepatic proinflammatory factors( P < 0. 05); HE staining suggested necrosis of a large number of hepatocytes,a decreased proportion of hepatic NK cells,reduced expression of NKG2 D,and increased expression of Ly49 A in the model control group( P < 0. 05). Poly I∶ C improved the serum levels of liver function indices,reduced the levels of intrahepatic proinflammatory factors,significantly improved liver inflammation,and increased the proportion and number of hepatic NK cells and expression of NKG2D( P < 0. 01). Conclusion Poly I∶ C can protect the liver from acute and chronic liver injury,and its mechanism of action is closely related to activation of NK cells.