Most vascular endothelial cells are continuously exposed to shear stress in vivo. Caveolae are omega-shaped membrane invaginations in endothelial cells (ECs) and are enriched in cholesterol, caveolins, and signaling molecules. This study was designed to elucidate the ultrastructural localization and change in caveolin-1 expression within human liver sinusoidal endothelial cells (LSECs) during the progression of cirrhosis caused by hepatitis C, using tissue sections prepared via perfusion-fixation. Normal control liver specimens and hepatitis C–related Child-Pugh A and C cirrhotic liver specimens were studied. Caveolin-1 in the liver sinusoids was examined via immunohistochemistry, Western blotting, and immunoelectron microscopy. In control liver tissue, caveolin-1 was localized on caveolae mainly in arterial and portal endothelial cells of the portal tract and was also found on vesicles and some fenestrae in LSECs around the central vein. In cirrhotic liver tissue, aberrant caveolin-1 expression was observed on caveolae-like structures in LSECs. Caveolin-1 was especially overexpressed in late-stage cirrhosis. This study demonstrates that caveolin-1 is strongly expressed within caveolae-like structures and associated vesicles within LSECs of the hepatitis C–related cirrhotic liver. These findings suggest a direct association of caveolin-1 in the process of differentiation of LSECs in cirrhosis-mediated capillarization.