Abstract: The research work was conducted to investigate the effect of intragastric administrations (five days a week) of praziquantel in a dose of 142mg kg-1 body weight (bw) for 85 days and black pepper in doses of 160 and 320 mg kg-1 bw for 36, 71, and 99 days on liver contents of DNA, total proteins, number and size of the liver cells and histopathological changes in the liver tissues of male and female albino rats. Non-significant changes were revealed that regarding the effect of both praziquantel, on DNA and cell numbers, and black pepper, on all the studied parameters, in male and female groups. Significant increase in liver total proteins and cell size was observed after praziquantel treatments. Modulating potential effect of black pepper, in a dose of 160mg kg‾1 bw, on the changed hepatic aspects induced by praziquantel was proved. Hepatic histopathological studies also showed lower percentage of animals manifesting moderate pathological changes in the group of animals treated with black pepper 160 mg kg‾1 bw followed by praziquantel 142mg kg‾1 bw when compared to the praziquantel group. The higher dose of black pepper showed the moderate and marked hydropic degeneration and portal tract inflammation throughout the used intervals in both male and female groups. The tested doses of praziquantel and black pepper throughout the used intervals could not cause malignant transformation, necrosis, or fatty degeneration.