AIM: Chronic organ-donor shortage has led to the acceptance of steatotic livers for transplantation, despite the higher risk of graft dysfunction or nonfunction associated with the ischemic preservation period of these organs. The present study evaluates the effects of trimetazidine (TMZ) on an isolated perfused liver model.METHODS: Steatotic and non-steatotic livers were preserved for 24 h in the University of Wisconsin (UW)solution with or without TMZ. Hepatic injury and function (transaminases, bile production and sulfobromophthalein (BSP) clearance) and factors potentially involved in the susceptibility of steatotic livers to ischemia-reperfusion (I/R) injury, including oxidative stress, mitochondrial damage, microcirculatory diseases, and ATP depletion were evaluated.RESULTS: Steatotic livers preserved in UW solution showed higher transaminase levels, lower bile production and BSP clearance compared with non-steatotic livers.Alterations in perfusion flow rate and vascular resistance,mitochondrial damage, and reduced ATP content were more evident in steatotic livers. TMZ addition to UW solution reduced hepatic injury and ameliorated hepatic functionality in both types of the liver and protected against the mechanisms potentially responsible for the poor tolerance of steatotic livers to I/R.CONCLUSION: TMZ may constitute a useful approach in fatty liver surgery, limiting the inherent risk of steatotic liver failure following transplantation.