The aim of this study was two fold; firstly we evaluate the influence of Hepatitis C virus (HCV) and iron deposition on hepatic stellate cells (HSC) and secondly we determine the influence of HSC’s on the development of interstitial fibrosis (IF) in renal allografts. Thirty chronic HCV patients with renal allografts were studied. Liver biopsies were scored for iron deposition and the number of HSC’s in the liver was evaluated by smooth muscle alpha-actin α-SMA) immunostaining. Also the distribution and the density of TNF- α in liver biopsies and the distribution of TGF-β on tubules in renal allografts of same patients were evaluated immunohistochemically. The influence of HSC’s on the development of IF during 12, 24 and 36 months after transplantation in renal allografts were evaluated. The HSC’s was significantly higher in HCV patients than in normal controls and the density of HSC’s were significantly higher in patients with iron deposits compared with those without iron deposits p<0.01). TNF- α expression was localized mainly in liver sinusoidal cells and in some cases it was also expressed in hepatocytes. Patients with higher grade TNF- α expression in liver showed higher grade of α-SMA positive HSC’s (p<0.001). In parallel to these, with increasing amount of HSC’s in the liver, the incidence of the development of IF in renal allografts during 12 (p<0.01), 24 (p<0.01) and 36 (p<0.05) months after transplantation was found increased. In addition the expression of TGF-β on tubules in renal allografts were found increasing grade of α-SMA positive HSC’s in liver (p<0.01). HCV infection and iron deposits in liver induce TNF- α expression and in turn activated HSC’s. Activated HSC’s had positive correlation with tubular TGF-β expression. In conclusion HCV infection has a triggering effect on development of IF in renal allografts by augmenting secretion of TGF-β through activating HSC’s.