Radiation-induced liver disease is recorded as a form of veno-occlusive disease. Its pathogenesis remains unclear even if the initial injury likely occurs in the endothelial cells of central veins. The aim of our study was to investigate liver morphological features in relation to α-isoform of smooth muscle actin expression in hepatic stellate cells in six patients treated by localized radiotherapy on the biliopancreatic area. Within the month after completion of treatment, an activation of hepatic stellate cells strictly confined to irradiated areas and coinciding with congestive changes was observed. At a later stage, collagen deposition gradually increased, replacing the congestive and destroyed areas. This new fibrotic tissue also contained numerous α-smooth muscle positive cells. Our data suggest that early hepatic stellate cells activation coinciding with congestive changes plays an important role in radiation liver injury and ensuing fibrosis.