Aim:Liver fibrosis represents a process of healing and scarring in response tochronic liver injury.Effective therapies for liver fibrosis are lacking.Interleukin-10(IL-10)is a cytokine that downregulates pro-inflarnmatory responses and has amodulatory effect on hepatic fibrogenesis.The aim of this study was to investi-gate whether electroporative IL-10 gene therapy has an hepatic fibrolytic effect onmice.Methods:Hepatic fibrosis was induced by administering carbon tetrachlo-ride(CCl_4)for 10 weeks in mice.The human IL-10 expression plasmid was deliv-ered via electroporation after hepatic fibrosis was established.Histopathology,reverse transcription polymerase chain reaction(RT-PCR),immunoblotting,andgelatin zymography were used to investigate the possible mechanisms of actionof IL-10.Results:Human IL-10 gene therapy reversed CCl_4-induced liver fibrosisin mice.RT-PCR revealed that IL-10 gene therapy attenuated liver TGF-β1,col-lagen α1,fibronectin,and cell adhesion molecule mRNA upregulation.Followinggene transfer,both the activation of(x-smooth muscle actin and cyclooxygenase-2were significantly attenuated.Furthermore,IL-10 significantly inhibited matrixmetalloproteinase-2(MMP-2)and tissue inhibitors of matrix metalloproteinase(TIMP)activation after CCl_4 intoxication.Conclusions:We demonstrated that IL-10gene therapy attenuated CCl_4-induced liver fibrosis in mice.IL-10 preventedupregulated fibrogenic and pro-inflammatory gene responses.Its collagenolyticeffect may be attributed to MMP and TIMP modulation.IL-10 gene therapy maybe an effective therapeutic modality against liver fibrosis with potential clinicaluse. Aim: Liver fibrosis represents a process of healing and scarring in response to tochronic liver injury. Effective therapies for liver fibrosis are lacking. Interleukin-10 (IL-10) is a cytokine that downregulates pro-inflamatory responses and has amodulatory effect on hepatic fibrogenesis. The aim of this study was to instisti-gate whether electroporative IL-10 gene therapy has an hepatic fibrolytic effect on mouse. Methods: Hepatic fibrosis was induced by chemical carbon tetrachlo-ride (CCl_4) for 10 weeks in mice. Human IL-10 Expression plasmid was deliv-ered via electroporation after hepatic fibrosis was established. Histopathology, reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and gelatin zymography were used to investigate the possible mechanisms of action of IL-10.Results: Human IL- 10 gene-reversed-CCl_4-induced liver fibrosisin mice. RT-PCR revealed that IL-10 gene therapy attenuated liver TGF-β1, col-lagen α1, fibronectin, and cell adhesion molecule mRNA upre Both the activation of (x-smooth muscle actin and cyclooxygenase-2were marked attenuated. Thermal Thermase, IL-10 significantly inhibited matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase (TIMP) activation after CCl_4 intoxication .Conclusions: We demonstrated that IL-10 gene therapy attenuated CCl_4-induced liver fibrosis in mice. IL-10 preventedupregulated fibrogenic and pro-inflammatory gene responses. Its collagenolytic effect may be attributed to MMP and TIMP modulation. IL-10 gene therapy maybe an effective therapeutic modality against liver fibrosis with potential clinicaluse.