Objective: Aspartame is a widely used artificial sweetener that was approved by the United States Food and Drug Administration (FDA) in 1996 for use as a general sweetener in all foods. Previous studies on aspartame had suggested it to be non-toxic. However, some studies have reported it to have carcinogenic, neurotoxic, apoptotic, and inflammatory effects. The knowledge obtained from previous studies has been insufficient and contradictory, thus the aim of this study was to demonstrate the harmful side effects of daily and high doses of aspartame on the rat livers. Materials and Methods:The study separated 18 Long Evans rats weighing between 250-300g into three groups: control, low dosage, and high dosage groups (n = 6 in each). 50 mg/kg of aspartame was given to the low dose group and 250 mg/kg to the high dose group every day for 10 weeks. At the end of the 10 th week, all groups were euthanized and their livers and blood samples collected. Liver tissues were subjected to hematoxylin-eosin and Masson's trichome staining, after which terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunohistochemistry was performed to check the serum alanine transaminase (ALT) and aspartate transaminase (AST) values. The enzymelinked immunosorbent assay (ELISA) method was applied for analyzing superoxide dismutase (SOD) and malondialdehyde (MDA) levels.Results: Enlargement of the bile canaliculi and dilatation of sinusoids were observed in the group that was given high doses of aspartame. At the same time, the amount of TUNEL-positive cells was higher in the high dose group. AST, ALT, and MDA values were increased while SOD values were decreased in both the low and high aspartame dosage groups. Conclusion:This study has concluded the prolonged use of high doses of aspartame to be able to cause damage to hepatocytes by stimulating oxidative stress, hepatocyte apoptosis, and necrosis.