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To elucidate the role of Kupffer cells in liver \ufb01brosis and cirrhosis, rats were treated with gadolinium chloride (GdCl<jats:sub>3<\/jats:sub>) and cirrhosis was induced by subchronic carbon tetrachoride (CCl<jats:sub>4<\/jats:sub>) administration. Carbon tetrachloride was administered three times per week for 8 weeks to male Wistar rats treated simultaneously with GdCl<jats:sub>3<\/jats:sub> (20 mg kg<jats:sup>\u22121<\/jats:sup>, i.p. daily); appropriate controls were performed. Serum enzyme activities of alkaline phosphatase (ALP), \u03b3\u2010glutamyl transpeptidase (<jats:italic>\u03b3<\/jats:italic>\u2010GTP) and alanine aminotransferase (ALT) and bilirubin concentration increased signi\ufb01cantly by CCl<jats:sub>4<\/jats:sub>, whereas GdCl<jats:sub>3<\/jats:sub> prevented completely the increase in <jats:italic>\u03b3<\/jats:italic>\u2010GTP and partially prevented the increase in ALP, ALT and bilirubins (<jats:italic>P<\/jats:italic> &lt; 0.05). Liver glycogen was depleted by CCl<jats:sub>4<\/jats:sub>, an effect that GdCl<jats:sub>3<\/jats:sub> was not capable of preventing. Moreover, gadolinium by itself depleted it. Lipid peroxidation increased about 2.5\u2010fold by administration with CCl<jats:sub>4<\/jats:sub>, whereas GdCl<jats:sub>3<\/jats:sub> preserved lipid peroxidation within normal values. Hepatic collagen increased threefold after subchronic intoxication with CCl<jats:sub>4<\/jats:sub> (<jats:italic>P<\/jats:italic> &lt; 0.05) whereas GdCl<jats:sub>3 <\/jats:sub>prevented partially (<jats:italic>P<\/jats:italic> &lt; 0.05) the increase in collagen content, as evidenced by the liver hydroxyproline content and by the histopathological analysis. The present results suggest that Kupffer cells are needed for the production of CCl<jats:sub>4<\/jats:sub>\u2010induced cirrhosis, because their inactivation with GdCl<jats:sub>3 <\/jats:sub>prevents the disease. 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