Liver cirrhosis is a major cause of morbidity and mortality worldwide. There is evidence indicating that liver cirrhosis is dynamic and can be bidirectional, involving phases of progression and regression, along with major changes in the regulation of matrix degradation. There is also evidence that Kupffer cells participate in both fibrogenesis and fibrolysis. This study was aiming to determine the effect of inhibition of Kuppfer cells by gadolinium chloride (GdCl3) on CCl4-induced liver cirrhosis in male balb-c mice. GdCl3 injected i/p at dose of 10 mg /kg dissolved in normal saline, three times per week for 2weeks, after injection of mice with CCl4 i/p at dose of 0.4 ml /kg (v/v) with olive oil twice per week for 6 weeks. The rise in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in CCl4-intoxicated mice was markedly suppressed by GdCl3 and histopathological changes were reduced and the expression of transforming growth factor β (TGF-β1) and Kupffer cells marker (CD68) were reduced in GdCl3treated mice. The results of this study indicate that activated Kupffer cells are involved in both process of fibrogensis as they could release cytotoxic mediators outside the cell that cause hepatocyte damage and fibrinolysis through release of gelatinases enzyme.