The commonly using of antibiotics and other chemotherapeutics for controlling diseases has been criticized with negative impacts in recent years. Therefore, many attempts have been looked forward to finding alternatively effective method in activating immunostimulatory of fish. Here, we investigated the effect of levamisole - enrich diets on striped catfish (Pangasianodon hypophthalmus) innate immune mechanisms (e.g., red blood cells, white blood cells, lysozyme activity and disease resistance). Different concentrations (50, 150, 300 and 450 mg/kg) and control (without levamisole) incorporated with fish feed for a period of 4 weeks. Experimental fish were challenged intra-peritoneally with Edwardsiella ictaluri on 28^th day. Hematological parameters were determined on the day 14 and 28. Total erythrocyte, monocytes, neutrophils and thrombocyte were increased in levamisole supplemented groups when compare with control group. The immunological parameter, lysozyme activity was statistically increased at doses of 150 and 300 mg/kg of the levamisole supplemented diet after 2 weeks (p>0.05). However, the innate immune response of levamisole groups were decreased lightly at 4^th week. Survival percentage post- challenged was found highest at the group of 300mg/kg and showed statistical difference when compare with the control group (p>0.05). This study reports that administration of levamisole could positively enhance innate immune response in striped catfish and resistance to E. ictaluri.