Background: Altered intestinal permeability values (IP) and intestinal ultra-structural abnormalities have been shown in cirrhotic patients as well as other liver diseases. Aims: To study the IP, serum levels of the intestinal tight junction (tj) modulator zonulin (Z), and the immunohystochemical [immunohistochemical] expression of junctional proteins occludin, claudin, desmoglein and intracellular actin in duodenal mucosa of HCV-CH patients. Methods: The Intestinal Permeability was evaluated by the Lactulose/Mannitol (LA/MA) test. Serum Zonulin levels were determined by sandwich-ELISA. Distal duodenum biopsies were obtained by EGDS and processed for immunohystochemistry [immunohistochemistry]. Staining was obtained with antibodies specific for occludin, claudin-4, desmoglein-3, and citoskeleton of actin. Conclusions: The increased Intestinal Permeability was detected in 32% of the HCV-CH patients studied and was associated to elevated serum Zonulin levels values. These changes were associated to modification of tj proteins expression and localization. Our data suggest that in a subgroup of HCV-CH patients the up-regulation of intestinal permeability-zonulin dependent may lead to increased non-self antigens access that may influence the course of the liver disease.