Catfish Clarias lazera (C. gariepinus) was used to study the effect of aqueous lupine seed suspension (ALSS) (Lupinus termis) on normal or treated fish with alloxan or glucose after 5, 24 and 4 days. Injection of alloxan was followed by hyperglycemia, hyperlipidemia, hypercholesterolemia, and rise in serum levels of total free amino acids (TFAA), AST and ALT compared with control. In liver, alloxan significantly reduced glycogen and total lipid/triglyceride ratio, while it accumulated lipids and elevated AST and ALT compared with control values. Also, alloxan induced lipid and glycogen depletion in red and white muscles. However, all disturbances in these parameters were restored to normal after ALSS administration. In glucose-treated fish, ALSS significantly increased glycogen content in white and red muscles. Also, glucose plus ALSS treatment increased red muscle contents of TFAA, total lipids and triglycerides. ALSS treatment did not induce any histological changes in liver. Both glucose and alloxan treatments induced damage effect on liver besides, ultrastructural alterations in the liver were observed. Furthermore, histochemical observation revealed a high liver glycogen following repeated glucose doses, while liver glycogen was depleted in response to alloxan injection. Alloxan induced necrosis, mitochondrial damage, few ribosomes on the surface of rough endoplasmic reticulum (rER) with disrupted cisternae in liver cells. Repeated doses of glucose injection for 4 days led to necrosis, clumps of rarefied cytoplasm as well as some cisternae of rER appeared to be devoid of ribosomes. However, most histological and ultrastructural changes in the liver were restored to normal after ALSS administration. In conclusion, it could be suggested that the lupine seeds have a protecting effect against both metabolic disturbances and damaging effect on liver cells in response to repeated doses of glucose or to alloxan treatments.