AIM:To investigate the pathway via which 17β-estradiol(β-Est) exerts suppressive effects on rat hepatic fibrosis.METHODS:In vivo study was done in CCl_4-induced femalehepatofibrotic rats.Fibrosis-suppressive effect of β-Est(20μg/kg·d) was evaluated in intact and ovariectomizedrat models.Six weeks after the treatment,all the ratswere sacrificed and specimens of serum or liver tissuewere collected for the studies.Serum liver enzymes,fibrosis markers and estradiol levels were determined bystandard enzymatic methods,ELISA and RIA,respectively.Degrees of fibrosis and areas of hepatic stellate cells(HSCs) positive for alpha-smooth muscle actin (α-SMA) inthe liver were determined by van Gieson (VG) stain andimmunohistochemistry.In vitro studies,HSCs were isolatedby a combination of pronase-collagenase perfusion anddensity gradient centrifugation.First-passage HSCs wererandomly divided into 10 groups,and different concentrationsof β-Est,2-hydroxyestradiol (2OHE) or 2-methoxyestradiol(2MeOE) were separately added to the cell groups.Afterincubation for 72h,the degree of cell proliferation,collagenproduction,α-SMA or estrogen receptor (ER) expression wasdetermined by MTI- assay,ELISA and immunohistochemistry,respectively.RESULTS:β-Est treatment reduced aspartate aminotransfer-ase (AST),alanine aminotransferase (ALT),hyaluronic acid(HA) and type Ⅳ collagen (C Ⅳ) in sera,suppressed hepaticcollagen content,decreased the areas of HSCs positive forα-SMA significantly in both intact and ovariectomized femalehepatofibrotic rats.There was a negative correlationbetween the percentage of fibrotic area of liver tissue andthe serum estradiol level;the calculated correlationcoefficient was -0.57 (P<0.01).β-Est and its metabolitesconcentration-dependently (10~(-9)mol/L-10~(-7)mol/L) inhibitedHSC proliferation and collagen synthesis.At the concentrationof 10~(-7)mol/L,they could inhibit α-SMA expression.Theorder of potency was 2MeOE>2OHE>β-Est.CONCLUSION:β-Est may suppress hepatic fibrosis probablyvia its biologically active metabolites. AIM: To investigate the pathway via which 17β-estradiol (β-Est) exerts suppressive effects on rat hepatic fibrosis. METHODS: In vivo study was done in CCl 4 -induced female patients withibrotic rats. Fibrosis-suppressive effect of β-Est · D) was evaluated in intact and ovariectomizedrat models.Six weeks after the treatment, all the ratswere sacrificed and specimens of serum or liver tissuewere collected for the studies .Serum liver enzymes, fibrosis markers and estradiol levels were determined by standard enzymatic methods, ELISA and RIA, respectively. Degrees of fibrosis and areas of hepatic stellate cells (HSCs) positive for alpha-smooth muscle actin (α-SMA) inthe liver were determined by van Gieson (VG) stain and immunohistochemistry. In vitro studies, HSCs were isolated by a combination of pronase-collagenase perfusion and intensity gradient centrifugation. First-passage HSCs were randomly divided into 10 groups, and different concentrations of β- Est, 2-hydroxyestradiol (2OHE) or 2-methoxyestradiol eOE) were separately added to the cell groups. Afterincubation for 72h, the degree of cell proliferation, collagenproduction, α-SMA or estrogen receptor (ER) expression wasdetermined by MTI-assay, ELISA and immunohistochemistry, respectively .RESULTS: β-Est treatment reduced aspartate aminotransfer-ase (AST), alanine aminotransferase (ALT), hyaluronic acid (HA) and type IV collagen (C IV) in sera, suppressed hepaticcollagen content, decreased the areas of HSCs positive for α- SMA significantly in both intact and ovariectomized femalehepatofibrotic rats. There was a negative correlation between the percentage of fibrotic area of ​​liver tissue and the serum estradiol level; the calculated correlation coefficient was -0.57 (P <0.01) .β- Est and its metabolites concentration- dependently (10 ~ (-9) mol / L-10 ~ (-7) mol / L) inhibited HSC proliferation and collagen synthesis. At the concentration of 10 ~ (-7) mol / L, they could inhibit α-SMA expression.Theorder of potency was 2MeOE> 2OHE> .CONCLUSION: β-Est may suppress hepatic fibrosisprobablyvia its biologically active metabolites.