This study was designed to estimate the pathological aspects of hepatotoxicity and fibrosis of the liver using Thioacetamide (TAA)  and the hepatoprotective effects of Silymarin in rabbits via biochemical tests and histopathological changes. A total of 24 male rabbits were used, randomly separated into 4 groups: Group I worked as a negative control, group II treatedwith Silymarin only by oral administration, group III was given IP injection TAA only, and finally  Group IV  was given TAA followed by Silymarin through oral route. Results revealed that rabbits treated with TAA had indicated a significant rise in total serum bilirubin, alkaline phosphatase, aspartate transaminase, and alanine transaminase levels. Histopathologically, liver sections showed severe centrilobular, periportal, hepatocellular vacuolation and necrosis respectively. Cholangitis with severe collagen fibres deposition was detected in the portal area accompanied by biliary duct epithelium hyperplasia and ductal fibrosis. The treatment with Silymarin followed by  TAA exposure leads to enhancement of both biological parameters and pathological features of the liver in Group IV. Finally, the present study concludes that Silymarin has a hepatoprotective and anti-fibrotic activity mechanism.