Mulberry extracts are antidiabetic and antihyperlipidemic, as well as preventive of cardiovascular disease. The current study investigates the protective mechanisms of mulberry water extracts (MWEs) in carbon tetrachloride (CCl 4 )-induced hepatic injury. Oral administration of MWEs significantly reduced the lipid peroxidation triggered by CCl 4 , as shown by the reduced production of thiobarituric acid-reactive substance (TBARS). The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were also reduced via cotreatment with MWEs compared with CCl 4 treatment alone. Cotreatment with MWE evidently reduced CCl 4 -induced liver weight and inhibited lipid deposition and fibrogenesis. In a similar manner, cotreatment with silymarin, a well-known liver protective agent, also reversed the CCl 4 -induced effects, such as reduced TBARS formation, decreased serum AST, ALT, and ALP levels, blocked lipid accumulation, and liver fibrosis. Furthermore, MWEs attenuated the proinflammatory genes such as cyclooxygenase 2, nuclear factor kappa B, and inducible nitric oxide synthase expression. The current findings suggest that MWEs such as silymarin exhibit protective and curative effects against CCl 4 -induced liver damage and fibrosis via decreased lipid peroxidation and inhibited proinflammatory gene expression.