Aim: In this study, the methanol stem bark extract of Detarium microcarpum was evaluated for sub-chronic, biochemical and histopathological studies. Methodology: Sub-chronic toxicity studies was investigated in rats administered with 35, 70 and 140 mg/kg doses of the extract orally for 28 days using standard laboratory procedures after the acute toxicity was carried out. Results: The median lethal dose (LD50) of the extract was calculated to be equal to (≥) 5000 mg/kg body weight in rats orally. Serological studies revealed significant (p<0.05) decrease in Alanine aminotransferase (ALT) at all doses tested, while at 140 mg/kg it caused a significant (p<0.05) increase in Alkaline Phosphatase (ALP). At doses of 70 and 140 mg/kg there was a significant (p<0.05) reduction in creatinine level. Histopathological studies on the liver showed moderate hepatocellular necrosis at doses of 35 and 70 mg/kg, while at 140 mg/kg there was intense hepatocellular necrosis,  Kupffer cells and lymphocytes hyperplasia. The Kidney showed intense necrosis of tubules and glomerular necrosis with lymphocytes hyperplasia at all doses tested.  The spleen also showed intense lymphocyte hyperplasia at all doses with sinusoidal congestion at the lowest dose of 35 mg/kg. The heart showed slight necrosis of cardiac muscle cells at all doses with blood congestion at 35 and 70mg/kg body weight. Conclusion: The study indicates that prolong use of the extract in the management of disease conditions may be associated with some adverse effect of some vital organs.