The effect of Levamisole on the immune response of 200 catfish (Clarias gariepenus) was evaluated. Fish were divided into 4 equal groups, reared in glass aquaria and fed on a basal diet. The 1st group served as a control. Fish of the 2nd group were fed Levamisole incorporated with diet (150mg/kg diet fed-1) for 2 months. The 3rd and 4th groups were vaccinated using Aeromonas hydrophila bacterin, at the first day of experiment, but fish of 4th group were fed on diet containing same dose of levamisole throughout the 2 months of experiment. At 1st, 3rd and 5th week, blood samples were collected from all groups for hematological, immunological and serum biochemistry studies while fish of 2nd group were subjected to histopathological investigations. Challenge was done to all groups, at 30th day of experiment, through immersion of fish in virulent Aeromonas hydrophila (1 g bacterial cells/liter) for 10 min, the mortalities recorded and the dead fish used for the bacterial re-isolation. Catfish of 1st group showed normal values throughout the period of the experiment. Fish of 2nd group showed activation of melanomacrophages. Hyperplasia of hematopoietic tissue was evident at 3rd-4th week. Degenerative changes were mild at 1st-2nd week and became prominent at 5th week. Fish of 3rd group showed a significant gradual increase of leucocytes, phagocytosis, antibody titer, total protein and globulin, at 1st-5th week post-vaccination. Fish of 4th group showed higher hematological and immunological values than those of 3rd group. The relative level of protection after the challenge infection was 30, 85 and 90% for the 2nd, 3rd and 4th groups; respectively. The histopathological finding of this experiment showed the safety of the selected dose of levamisole on catfish. The other findings indicate its efficiency as immunostimulant in improving the immune response of catfish to Aeromonas hydrophila vaccine.