Aim:To investigate the effects of a tissue-specific selective estrogen receptormodulator,idoxifene,on hepatic fibrosis in rats.Methods:Hepatic fibrosis wasinduced by dimethylnitrosamine(DMN)in male rats.The DMN model of hepaticfibrosis and the hepatocytes undergoing oxidative stress were treated withidoxifene respectively.The effect of idoxifene on hepatic fibrosis in the DMNmodel was examined by immunohistochemistry.Effects of idoxifene on antioxi-dant enzyme levels of copper,zinc-dependent superoxide dismutase(CuZn-SOD),and cellular glutathione peroxidase(GSHPx)were measured by ELISA.Effects ofidoxifene on activation,proliferation,and apoptosis of culture-activated hepaticstellate cells(HSC)were analysed by immunohistochemistry,bromodeoxyuridine(BrdU)uptake,and flow cytometry, respectively. Results:Idoxifene could mark-edly suppress DMN-induced hepatic fibrosis in male rats.A treatment of 0.4mg·kg~(-1)·d~(-1)of idoxifene reduced the protein levels of collagen in the DMN modelby 41.19%(P<0.05).Protein level of CuZn-SOD and activitiy of GSHPx in livertreated with DMN plus 0.4 mg.kg~(-1)·d~(-1)of idoxifene were 2.65 times(P<0.05)and2.08 times greater(P<<0.05)than that of liver treated with DMN alone respectively.The protein level of CuZn-SOD and activity of GSHPx in cultured rat hepatocytestreated with ferric nitrilotriacetate(FeNTA)plus 1×10~(-7)mol/L of idoxifene were3.43 times(P<0.05)and 2.52 times(P<0.05)greater than that treated with FeNTAalone.Idoxifene could inhibit HSC activation.Compared with the control,theuptake of BrdU in HSC cultured with 1×10~(-7)mol/L of idoxifene was reduced by51.87%(P<0.05),and the number of apoptotic HSCs cultured with 1×10~(-7)mol/L ofidoxifene increased by 94.52%(P<0.05).Conclusion:Idoxifene showed inhibi-tory action on hepatic fibrosis in male rats. Aim: To investigate the effects of a tissue-specific selective estrogen receptorormodulator, idoxifene, on hepatic fibrosis in rats. Methods: Hepatic fibrosis was induced by dimethylnitrosamine (DMN) in male rats. DMN model of hepatic fibrosis and the hepatocytes undergoing oxidative stress were treated withidoxifene respectively. The effect of idoxifene on hepatic fibrosis in the DMN model was examined by immunohistochemistry. Effects of idoxifene on antioxi-dant enzyme levels of copper, zinc-dependent superoxide dismutase (CuZn-SOD), and cellular glutathione peroxidase (GSHPx) were by ELISA. Effects of idoxifene on activation, proliferation, and apoptosis of culture-activated hepaticstellate cells (HSC) were analysed by immunohistochemistry, bromodeoxyuridine (BrdU) uptake, and flow cytometry, respectively. Results: Idoxifene could mark-edly suppress DMN-induced hepatic fibrosis in male rats. A treatment of 0.4 mg · kg -1 (-1) of idoxifene reduced the protein levels of collagen in the DMN model by 41. (P <0.05) .Protein level of CuZn-SOD and activitiy of GSHPx in livertreated with DMN plus 0.4 mg · kg -1 · d -1 idoxifene were 2.65 times (P <0.05) and 2 .08 times greater (P << 0.05) than that of liver treated with DMN alone respectively.The protein level of CuZn-SOD and activity of GSHPx in cultured rat hepatocytestreated with ferric nitrilotriacetate (FeNTA) plus 1 × 10-7 mol / L of idoxifene were 3.43 times (P <0.05) and 2.52 times (P <0.05) greater than that treated with FeNTAalone. Idoxifene could inhibit HSC activation. Compared with the control, the uptake of BrdU in HSC cultured with 1 × 10 (-7) mol / L of idoxifene was reduced by 51.87% (P <0.05), and the number of apoptotic HSCs cultured with 1 × 10 ~ (-7) mol / L of idoxifene increased by 94.52% ) .Conclusion: Idoxifene showed inhibi-tory action on hepatic fibrosis in male rats.