In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl₄ at a dose of 1 mL/kg, i.p. was investigated in experimental rats. Ten days of preventive treatment with aminoguanidine before exposure to toxic CCl₄, at a dose of 150 mg/kg, i.p., led to significant reduction in biochemical markers of acute liver injury-AST(p < 0.001), ALT (p < 0.01), SDH (p < 0.05) and reduction in pro-oxidative markers-H₂O₂ (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl₄. Treatment with aminoguanidine resulted in a significant reduction in the consumption of antioxidant-GR (p < 0.01), GST, GPx, GSH (p < 0.001), and a decrease in pro-inflammatory-TNF-α (p < 0.01), IL-1β, IL-6, NO and NGAL (p < 0.001) markers relative to animals exposed to CCl₄ alone. Also, aminoguanidine pre-treatment leads to an increase in arginase activity (p < 0.001), and a decrease in citrulline concentration (p < 0.01), as well as polyamine catabolism enzyme activity-putrescin oxidase and spermine oxidase (p < 0.001) in comparison to the CCl₄ group. Aminoguanidine led to a striking reduction of the necrotic field (p < 0.001), and a significant increase in the number of apoptotic hepatocytes (p < 0.001), as well as the proapoptotic markers-BAX and Caspase-3 (p < 0.05), compared to CCl₄. The hepatoprotective mechanisms in CCl₄ induce hepatotoxicity of aminoguanidine are based on the strong antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, as well as induction of damaged hepatocytes into apoptosis.