In the current research, Oreochromis niloticus fish were subjected to experimental infection by Aspergillus flavus and treated by the garlic powder (immunostimulants) in the feed. The infected fish exhibited signs of protrusive eye, slow-motion, lethargy, skin covered by thick mucus, severe hemorrhage on dorsal, anal and caudal fins, discarded scales and caudal fin erosion. Postmortem examination revealed that accumulative of bloody fluids in viscera and the abdominal cavity, damaged liver and enlargement of gall bladder which was filled with bile. Treatment trials exerted zero mortality with Allium sativum (garlic) but group treated by Aspergillus flavus with Allium sativum the mortality rate was 20% while the mortality rate was 100% with Aspergillus flavus group . Hematological picture showed normocytic normochromic anemia in both Aspergillus flavus and Aspergillus flavus with Allium sativum treated groups. Leucopenia and lymphopenia observed in Aspergillus flavus group, while lymphocytosis was reported in Allium sativum treatment group. There were significant increase in liver transaminases enzymes (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) and decrease in total protein and albumin level in Aspergillus flavus but in Aspergillus flavus with Allium sativum significantly reversed the biochemical changes in the blood serum AST, ALT , total protein and albumin level. Histopathological findings of gills in fish group that was infected with Aspergillus flavus were severe in forms of proliferation of the filamentary epithelium leading to lamellar fusion of the secondary lamellae and desquamation, particularly at the tips and the pathological changes in the liver showed severe blood congestion and hemolytic with clear diffusion of melanomacrophage (MMC), thrombosis in blood vessels and severe congestion in pancreatic acini. These lesions may become less severe in fish of Aspergillus flavus with Allium sativum group. It could be concluded that the safety and useful dietary addition of Allium sativum (garlic) to alleviate the effects of Aspergillus flavus on Oreochromis niloticus fish.