Liver fibrosis is a hallmark of clonorchiasis suffered by millions people in Eastern Asian countries.However,little is known to date about the expression of transforming growth factor-β(TGF-β)and other molecules in TGF-β/Smad signaling pathway which may play an important role in hepatic fibrosis caused by C.sinensis.A total of 24 mice were individually infected orally with 45 metacercariae,both experimental mice(n=8)and mocked-infected control mice(n=5)were anesthetized at 4 week post-infection(wk p.i.),8 wk p.i.,and 16 wk p.i.,respectively.For each time-point,the liver and serum from each animal were collected to analyze histological findings and various fibrotic parameters including TGF-β1,TGF-β receptors and down-stream Smads activation,as well as fibrosis markers expression.The results showed that collagen depositions indicated by hydroxyproline content and Massons trichrome staining were increased gradually with the development of infection.mRNA levels of Smad2,Smad3 as well as the protein of Smad3 in livers of C.sinensis-infected mice were increased after 4 wk p.i.(P<0.05,compared with normal control)whereas the TGF-β1,TGF-β type Ⅰ receptor(TGFβRI)and TGF-β type Ⅱ receptor(TGFβRⅡ)mRNA expression in C.sinensis-infected mice were higher than those of normal control mice after 8 wk p.i.(P<0.05).However,the gene expression of Smad4 and Smad7 were peaked at 4 wk p.i.(P<0.05),and thereafter dropped to the basal level at 8 wk p.i.,and 16 wk p.i.,respectively.The concentrations of TGF-β1 in serum at 8 wk p.i.and 16 wk p.i(P<0.05)were significantly higher than in the control mice.The results of the present study indicated for the first time that activation of TGF-β/Smad signaling pathway may be involved in liver fibrosis caused by C.sinensis.