Background: the aim of this study is to identify the toxic effect of gemcitabine on the kidney and liver tissues of rat and whether melatonin has any protective effect on these tissues.
 MATERIALS AND METHODS: 32 adults male Wistar rats were selected and divided into four groups. Group A was the control group that received normal saline. Group B received gemcitabine alone in a dose of 25mg/kg body weight intraperitoneally once per week for four successive weeks. Group C received gemcitabine intraperitoneally in a dose of 25mg/ kg and melatonin orally in a dose of 10mg/kg once per week for four successive weeks. Group D received only melatonin 10mg/kg once per week for four weeks.
 RESULTS: The histological changes of liver of group B showed disorganization of hepatic tissue with congestion in the portal area and chronic inflammatory cells infiltration in the periportal area. Nuclei of some hepatocytes were vesicular with steatosis. In group C liver sections showed inflammatory cell infiltration with mild pyknosis of some hepatocytes. Liver sections of group D were limited to degeneration of some hepatocyte. Renal sections of group B showed degeneration and necrosis of epithelial cells with thickening of blood vessel wall, congestion and thrombus formation with cystic appearance in the interstitial tissue were detected. While in group C the histological sections showed swelling of epithelial cells lining renal tubules with congestion of blood vessels. Renal sections of group D were more or less normal.
 CONCLUSION: the present study concluded that gemcitabine induced toxic effect on liver and kidney of male rats and melatonin may play protective effect on the tissue of these organs.
 Key wards: gemcitabine, melatonin, liver, kidney, rat