It is well established that CCl₄ induce liver injury in animals through production of free radicals and oxidative stress, and subsequent lipid peroxidation that propagates injury. The aim of the present study was to evaluate the effect of aqueous extract of silybum marianum (SB) plant relative to silymarin (SM) as standard drug on liver enzymes, cytochrome P450 (CYP450), and histological changes using H&E and atomic force microscope (AFM). The aqueous extract of SB was prepared and the determination of total phenolic compounds in aqueous extract of silybum marianum and in silymarin standard drug was done. Results showed that CCl4was found to induce liver injury by significant increase in alanine transaminase (ALT), aspartate amino transferase (AST), and alkaline phosphatase (ALP), malondialdehyde (MDA), and CYP450 which were confirmed using H&E and atomic force microscope (AFM) while decreasing albumin (ALB) and activates of glutathione -S- transferase (GST), glutathione reduced (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC). Whereas, treatment with aqueous extract of SB as well as SM drug significantly decrease ALT, AST, ALP and MDA and increased ALB, GST, GSH, SOD, CAT, TAC levels as well as decreasethe level of CYP450. In conclusion, aqueous extract of SB ameliorates the toxic effects of CCl₄ by its free radical-scavenging and potent antioxidant activity and can be used for the treatment of liver injury.