Inhibition of Kupffer cells could disrupt the sequence of events leading to organ injury by damping down the ﬁbrogenic stimulus. To elucidate the role of Kupffer cells in liver ﬁbrosis and cirrhosis, rats were treated with gadolinium chloride (GdCl3) and cirrhosis was induced by subchronic carbon tetrachoride (CCl4) administration. Carbon tetrachloride was administered three times per week for 8 weeks to male Wistar rats treated simultaneously with GdCl3 (20 mg kg−1, i.p. daily); appropriate controls were performed. Serum enzyme activities of alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GTP) and alanine aminotransferase (ALT) and bilirubin concentration increased signiﬁcantly by CCl4, whereas GdCl3 prevented completely the increase in γ-GTP and partially prevented the increase in ALP, ALT and bilirubins (P < 0.05). Liver glycogen was depleted by CCl4, an effect that GdCl3 was not capable of preventing. Moreover, gadolinium by itself depleted it. Lipid peroxidation increased about 2.5-fold by administration with CCl4, whereas GdCl3 preserved lipid peroxidation within normal values. Hepatic collagen increased threefold after subchronic intoxication with CCl4 (P < 0.05) whereas GdCl3 prevented partially (P < 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 CCl4-induced cirrhosis, because their inactivation with GdCl3 prevents the disease. Published in 2003 by John Wiley & Sons, Ltd.