A process of assessing the effect of incorporating Cyanoprokaryota Anabaena wisconsinense on immunostimulant and enhancing fish resistance to pathogenic bacteria of Nile tilapia (Oreochromis niloticus) was conducted. One hundred and thirty five of all male O. niloticus (20 ± 2 g / fish) were randomly collected from stored earthen ponds of Abbassa fish farm, Sharkia, Egypt. The fish were acclimatized for two weeks, and then divided into 3 groups (45 fish / group); each in 3 replicates containing (15 fish per / glass aquaria) supplied with 210 liters of water. The first group (T₁) was fed with basal diet (crude protein 30%) containing 1% whole fresh cells of A. wisconsinense. The second group (T₂) was fed with the same basal diet containing 2% whole cells of A. wisconsinense. The third group (T₃) was fed with basal diet free from A. wisconsinense cells (control diet). Fish were hand-fed once daily in 28 days, at a rate of 3% of body weight. At the end of the feeding experiment, 90 fish were challenged (10 fish from each aquarium) with Aeromonas sabriia, Actinobacter anitratus and Aeromonas veronii and then kept under observation for 15 days. A significant increase in Haematocrit level was reported; respiratory burst and serum lysozyme activity among fish fed with diet containing (Cyanoprokaryota) compared to control fish. A. wisconsinense supplement decreased the total bacterial count in the intestine than control group and increased fish resistance to Aeromonas sabriia, Actinobacter anitratus and Aeromonas veronii.