The main histological and histochemical changes in the rat's liver tissue induced by intraperitoneal injection of 5-FU were investigated in this study. Twelve adult female rats were divided into two groups of 6 rats each, group I was given 2 ml/kg body weight of normal saline for 7 consecutive days and served as the control group, while group II was given 20 mg/kg of 5- fluorouracil intraperitoneally for 7 consecutive days. Specimens of the liver tissue from the two groups were taken and prepared for light microscopic examination. Results showed the appearance of some histological changes in the5-FU recipient group (group II) compared to the control group (group I) including congestion of central vein, dilatation and congestion of the hepatic sinusoids, vacuolar degeneration of the hepatocytes, loss of normal histological architecture of the liver, in addition to sever fatty changes and apoptosis of the hepatocytes. Histochemical examination of the liver of the treated group revealed a marked decrease in the carbohydrates including glycogen manifested as weak positive reaction to PAS and Best's carmine stains compared to the control group in addition to marked increase in the activity of alkaline phosphatase manifested as a strong reaction to Gomori's alkaline phosphatase stain as compared to the control group. We conclude that 5-fluorouracil has toxic effects on the liver tissue causing vacuolar degeneration of the hepatocytes, sever fatty changes and apoptosis.