Thioacetamide (TAA) is a well known hepatototoxic chemical that is used to induce liver cirrhosis similar to that occurred in human. This study was performed to investigate the possible protective effect of metformin against deleterious effects induced by thioacetamide in rat livers and to find out the possible mechanisms of action. Male rats were divided into 4 groups control group, TAA group received 300mg/L in drinking water for 12 weeks, metformin group received 50mg/kg/day by gavage for 12 weeks and co- treated group that received metformin 50mg/kg/day by gavage for 12 weeks in addition to TAA in the same previously mentioned dose for the same duration of time and started from the first day of metformin. The rats were weighted and euthanized. Liver tissues and blood samples were collected for estimation of key oxidative stress markers, liver enzymes and pro-inflammatory cytokine (TNF-α). The results showed that TAA induced massive functional and structural damage of the liver. Metformin treated rats significantly attenuated TAA induced changes in both liver function and structure with reduction in rises of malondialdehyde (MDA) and superoxide dismutase (SOD) levels in liver tissue with reduction in serum levels of TNF-α.  The liver weights (LW) and the liver/body weight ratios (LW/BW) in thioacetamide rats had significantly increased compared to the control rats. Metformin had significantly reduced liver weights and the liver/body weight ratios compared to thioacetamide rats. On conclusion: metformin attenuates the deleterious effects of thioacetamide on liver tissue and exhibits hepatoprotection against these effects through inhibition of peroxidation, inflammation and oxidative stress and enhanced antioxidant status in rat liver tissues suggesting the potential efficacy of metformin as an addition hepatoprotective, anti-inflammatory and anti-hepatotoxic agent in treatment of liver toxicity.