Abstract: The aqueous root-bark extract of Ficus sycomorus (Linn) was screened for its chemical constituents, median lethal dose and its histomorphological effect on the liver and kidney of albino rats. A total of 114 adult albino rats of both sexes weighing between 150-320 g were used in this study. The animals were weighed and randomly divided into two batches for the acute toxicity and histomorphological studies. In the acute toxicity study the aqueous extract of the root-bark of Ficus sycomorus was administered intraperitoneally (ip) in a dose range of 0.2-12 g kg-1 and the rats were observed for the physical signs of toxicity for 24 h. For the histomorphological effect of the extract on the liver and kidney 320, 640 and 1,280 mg kg-1 were administered to the rats for 2, 4 and 6 weeks, respectively. At the end of each treatment period, the animals were weighed before been sacrificed and the liver and kidneys were extracted, weighed and processed for histological assessment. Phytochemical screening of the extract showed the presence of saponins, flavonoids, alkaloids, tannins and reducing sugar while the median lethal dose (LD50 ) was calculated as 3.20±0.60 g kg-1. A significant decrease (p<0. 001) in body weight was observed but weights of kidney and liver treated with the extract were not affected significantly. Microscopic examination of the liver tissues of rats treated with the extract showed degenerative changes ranging from cytoplasmic vacuolation of hepatocytes, necrosis, dilatation of the central vein and proliferation of bile ducts. There was no observable effect on the kidney. The results of the study suggest that the extract possess hepatotoxic potentials and should be used with caution but a further research to assess the pharmacokinetics of the extract on cell membrane stability, lipid peroxidation, parenchymal cell regeneration and ultra structural study will be useful and is recommended.