The stem bark and leaves of Uapaca togoensis has been used in traditional medicine to treat fever, epilepsy, rheumatism, vomiting and fatigue. The present study was designed to evaluate the acute and sub-chronic toxicity profile of the methanol stem bark extract of Uapaca togoensis as there are no reported toxicological studies on the plant. Preliminary phytochemical screening revealed the presence of alkaloids, steroids, triterpenes, glycosides, tannins, saponins and flavonoids, however anthraquinones were absent. Acute toxicity test revealed no signs of toxicity however in the sub-chronic study, the extract at doses of 250, 500 and 1,000 mg/kg significantly (p<0.05) reduced body weight of the rats at the 3rd and 4th week of the study. A significant (p<0.05) increase in white blood cell levels at 500 mg/kg and 1,000 mg/kg and a significant (p<0.05) decrease in platelet levels at 1,000 mg/kg was noted. The extract significantly (p<0.05) increased low density lipoprotein, triglycerides, conjugated bilirubin and creatinine levels. At all doses, necrosis and degenerative changes were observed in the intestine, kidney, liver and spleen. The results from the acute toxicity study suggests the relative safety of the extract, however sub-chronic toxicity studies showed that prolonged use of the plant should be with caution. Keywords – Uapaca togoensis, Sub-chronic toxicity, Histopathology, Hematology, Serum biochemistry