The present study was planned to investigate the immunological changes in blood and mucus of catfish Clarias gariepinus infected with Pseudomonas florescence along with trial for control using (β-glucan). A total number of 240 catfish were collected from Ismailia channel and subdivided to 4 equal groups: the control group, infected group with virulent strain of P. florescence, β-glucan group and β-glucan infected group fed on diet supplemented with β-glucan. The blood and mucus samples were taken at 2 days, 3 and 5 weeks for immunological examinations. There were significant decreases in total protein and albumin of the infected group, while β-glucan and β-glucan infected groups revealed significant increases in total protein and globulin compared to the control group. The serum and mucus immunological studies revealed enhanced immune parameters (lysozyme activity and IgM) in all groups with non-significant change in protease level in serum but increased in mucus only compared to the control group. These results concluded that dietary supplementation of β-glucan enhanced skin mucosal and serum humoral defence responses and resistance of catfish againstinfection with P. florescence. The results could be useful for better understanding the role of skin mucus as a key component of the innate immune system, which could be beneficial in control of fish health.