Plants are the primary source of human medications and knowledge on its toxicity is vital; this work evaluates the acute toxicity and effect of Acacia nilotica leaf crude extract on the liver and kidney functions. The mean lethal dose (LD50) was determined by Lorke’s method, while the crude extract effect was evaluated by biochemical and histo-pathological assessments. The LD50 value was 3807.89 mg/kg for both oral and intra-peritoneal route of administrations. An elevated serum urea above the normal reference value in both control and treated group upon administration of 1000 mg/kg of the extract with mean values of 7.92 ± 1.19 and 7.86 ± 1.14 mmol/l respectively was observed. The results of ALAT, ASAT, ALP, T.protein, Albumin, and bilirubin in all cases were within the normal values. The kidney and liver function parameters at higher extract concentrations of 500 and 1000 mg/kg/day and relative organ weight were statistically significant (p< 0.05) and correlates with mild effect indicted on the histopathology of the organs. This study showed that administration of A. nilotica extract at 500 and 1000 mg/kg/day for an extended period could prompt hepatic and nephron toxicity
