Phaleria macrocarpa is used as a traditional medicine for a wide range of diseases including cancer, diabetes, liver disease, kidney disease, allergies and male infertility in Southeast Asia. The study evaluated the possible toxic effect of Phaleria macrocarpa fruit on the liver function by measuring liver enzymes and histopathological examination of liver tissue. Twenty-four male Sprague Dawley rats were allotted randomly to four groups including: control (no treatment), while the other three groups were administered Phaleria macrocarpa aqueous extract (750, 1500 and 3000 mg/kg bodyweight respectively). All administration was through intragastric gavage for 28 days. The liver enzymes measurement and histological study were done at the end of the administration using standard procedures. The results showed that the significant increase (p < 0.05) in body weight at the end of study compared to beginning of experiment was due to the normal growth. There was no significant difference in plasma aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) levels among groups. However, there was a significant increase (p < 0.05) in plasma alanine aminotransferase (ALT) and alkaline phosphatase (ALP) compared to control. Histopathological study showed that there were mild to severe changes of vacuolization and degeneration of tissues in treated groups which indicated the liver damage had occurred. Phaleria macrocarpa extract at dose of 3000 mg/kg body weight for a period 28 days caused mild toxicity effect to the liver tissue but its effect did not contribute to the changes in liver function of the rats.