In Sudan and other countries, Manihot esculenta roots (cassava) consumed mainly as flour after a traditional processing which we are suggesting that it's not enough to eliminate all cyanogenic glycoside (toxic compound). This study was carried out to evaluate the aqueous and methanolic extracts toxicity of Manihot esculenta (cassava) tubercular roots on Wistar rats after traditional processing in two weeks consumption. The plant was peeled and dried after that it was extracted using methanol and water. Wistar rats were allotted at random to five groups, each of 6 rats; four groups were given their designated dose of the extracts of both aqueous and methanol in two different dose orally which was 75 and 300 mg kg-1, the fifth group was control. The mortality and weight gain, serobiochemical and hematological parameters were recorded in addition to pathological changes. Demonstration of M. esculenta extracts orally result in alteration in (aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) activities, changes in the concentration of urea, cholesterol and other serobichemical parameters, pathological changes in fatal organs, including Necrosis and shrinkage of the glomeruli and aggregates of lymphocytes in the renal cortex was observed, this changes were accompanied with cytoplasmic fatty vacuolation of entrilobula hepatocytes and cerebral neurons. We conclude that Manihot esculenta is toxic causing alteration on various serobiochemical and hematological parameters, this toxicity was correlated to dysfunction of vital organs and we retained all consequence of toxicity to the presence of cyanoginc glycoside; linamarin and lotaustralin.