The role of the liver is the major site of detoxification and metabolism, so it was considered as a target organ in toxicological studies. The present study investigates the potential protective effects of Amphora coffeaeformis extract against hepatotoxic effects in African catfish, Clarias gariepinus induced by arsenic. The fish Clarias gariepinus was exposed to sub-lethal concentrations of arsenic; 19.2 and 38.3 mg/L (1/8 and 1/4 of 96h-LC50 value, 153.17 mg/L) for 15 days. Histopathological alterations of the liver were analyzed under light and transmission electron microscope (TEM). Using the light microscope, the alterations were hypertrophy and hyperplasia of hepatocytes, necrosis, melanomacrophage accumulation, lymphocytic aggregation and congested blood vessels as well as depletion in glycogen content. TEM investigation resulted in alterations in perichromatin granules that increased and progressively formed small clusters closely related with patches of heterochromatin. Also fractionation, dilation, and vesiculation of rough endoplasmic reticulum were observed in addition to mitochondrial hyperplasia, hypertrophy and cristolysis. Significant main effects were reported for glutathione and malondialdehyde levels (P< 0.05) after arsenic exposure. This arsenic-induced hepatotoxicity was improved with the dietary supplementation of Amphora. We concluded that Amphora extract can be used as a hepato-protective agent on arsenic-induced fish due to its biologically active components.