The aim of this study is to evaluate the effect of the concentrations (0.0, 0.5, 1.0, 2.0 and 4.0g/L) of the leaves of Azadirachta indica for seven (7) days on the serum enzymes acid phosphatase (ACP), alkaline phosphate (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of African catfish Clarias gariepinus which is widely cultured in Nigeria because of its remarkably fast growth rate and high market value. The level of serum ACP , ALP, ALT and AST revealed a significant decrease (P<0.05). In this study, the general inhibition of ALT, AST, ALP implies that there were hepatic disorders (liver disease) or renal injury, a disruption of the activity of the TCA cycle, respiratory process and glycolytic pathways. The present study, thus, tries to provide baseline information on the involvement of these biochemical parameters in toxicity assessment of aquatic system and also on the alteration of the enzymatic parameters maybe used in assessment of these plant extract.