The toxicity profile of the ethyl acetate (EA) extract of the stem bark of Cylicodiscus gabunensis (CG) was studied in Wistar rats. The rats were administered graded doses (0.75, 1.5, 3 and 6 g/kg p.o.) of the extract daily for 6 weeks and the effects on clinical signs, body weight, food and water consumption, organ weight, haematology, histology as well as serum, hepatic and renal biochemical parameters were measured. Body weight of dosed and control rats increase throughout the duration of treatment but food and water consumption were not significantly affected. The relative weights of the liver, lungs, heart and kidneys remained normal whereas a significant change was observed in that of the spleen. The hematocrit level was increased in treated animal. Our data demonstrates a significant increase in serum concentrations of aspartate amino-transferase, alanine amino-transferase, total cholesterol and glucose with high-dose of CG treatment tested (3-6 g/kg). CG also caused a significant reduction in hepatic malondialdehyde concentration. Renal urea and creatinine levels were reduced significantly in test groups. Histological findings reveal a characteristic progression treatment-related effect on liver, kidneys and lungs. The acute toxicity LD50 was estimated at 14.5 and 11 g/kg body weight (b.w.) for male and female respectively, but dose-related mortality of 30 and 50% were observed during the sub-acute toxicity. These findings have once more highlighted the limitations of the acute toxicity LD50 testing and suggest that CG may exert varied toxicological effects when administered orally in rats.