Histological alterations are used as indicators of aquatic pollutants and overall health of the entire population of organisms in an ecosystem. These histological parameters are related to other biomarker of stress since many pollutants have to undergo metabolic activation in order to be able to provoke cellular changes in the affected organism. Apparent healthy One hundred and twenty (120) juvenile of Clarias gariepinus, mean weight 9.77 ± 0.42g and mean length of 13.8 ± 0.80cm were used. Fish were placed in twelve (12) circular plastic tanks (40 × 30 × 20cm) and ten (10) fish were placed in each of the tanks and were allowed to acclimatize tolaboratory conditions for a period of 2 weeks during which the fish were fed with Vital feed® once daily at 3% of their body weight. The gills and liver were excised and processed, by using routine histological screening. Histological section through the gills and liver of C. gariepinus juveniles exposed to acute concentrations of aqueous crude fruit extract ofAcacia nilotica revealed some severe histological alterations such as complete loss of secondary lamellae, massive presence of inflammatory cells, and degeneration of connective tissue, hypertrophy and hyperplasia which increased as the toxicant concentration increased. The acute bioassay of aqueous crude fruit extract of A. nilotica on C. gariepinus juveniles revealed that the substance is toxic to the exposed fish at various concentrations and the result showed the 96hrLC50 caused 50% mortality. The toxicant had adverse effects on the water qualities, behavioral signs & histological parameters of the exposed fish compared to the control groups. The disruption in these parameters could have led to the degrees of impairment in the gills and livers of the exposed fish and the inability of the exposed fish to withstand infections, thereby causing a great concern for fish survival. Therefore, the use of Acacia niloticain water bodies could lead to contamination of aquatic ecosystem by causing alteration in the physiological and general health of fish and other aquatic fauna.