The challenge infection revealed a significantly lower mortality percentage in the group received 10 g/kg S. platensis in diet for the 1, 2 and 3 months feeding trial and significantly high relative level of protection (RLP) after challenge infection using P. fluorescens. The disease challenge is an in vitro technique provides an opportunity to determine the performance and immunity of the fish species ebon exposure to xenobiotic (bacteria) on their natural habitats (AraKoosh et al., 2009). The results were in accordance with Watanuki et al. (2006) who recorded an increased resistance of S. platensis treated carp ebon artificial challenge with A. hydrophila than the control group. Abdel-Tawwab and Ahmad (2009) found that SP has a useful impact on fish as immuno-stimulants, they recorded that tilapia fed 5-10 g fresh S. platensis /kg diet increased its resistance against A. hydrophyla. Finally, from the present investigation, it was concluded that optimized the dietary levels of dried Spirulina in O. niloticus, was useful to decrease costs of the products used and negate losses that could be encountered with improper supplementation levels. It was proved that the optimum concentration of dried S. platensis in the O. niloticus practical diet is 10 g/kg for 2 months, to positively improving health conditions, enhanced the non-specific immunity of Oreochromis niloticus, as well as its resistance to challenge by P. fluorescens infections. It is recommended to supplement Spirulina in the diet of Nile tilapia especially those grow in farms under immunosuppressive/stressful conditions. Additional researches are needed to study additional desired effects of the blue green algae in cultured fish.