The goal of the study is to examine the potentially harmful histopathological and biochemical effects of 5- Fluorouracil (5-FU) on the liver and kidney. Thirty rats were divided into two groups. The control group was given physiological saline intraperitoneally for 5 days. The 5-FU group received 5-FU at a dose of 20 mg/kg b. wt. intraperitoneally for 5 days. Blood samples were collected and used for biochemical indexes. For histological analysis, samples of the liver and kidney were collected. There was a significant increase in the levels of serum creatinine, urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), malondialdehyde (MDA( in the 5-FU group when compared to the control group. Compared to the control group, there was a significant decrease in total antioxidants (TAO). Microscopic examination of the liver showed vascular changes, apoptosis, vacuolar degeneration, kupffer cell proliferation, focal inflammatory cell infiltration, hepatocellular necrosis and mononuclear cellular infiltration in the portal area. While the histopathological changes in kidneys varied from vascular changes, glomerular necrosis and atrophy and vacuolar degeneration of the renal tubules. It was concluded that the hepatotoxic and nephrotoxic effects were due to the oxidative stress induced by 5-FU.