Frequent use of antimicrobial agents may result in bacterial generation resistant to multiple antibiotics that affect on public health hazard. Our Study aimed to isolation of Edwardesiella species from fresh Oreochromis niloticus and Claris gariepinus(50 of each ) which were collected from fish farms and markets in Kafrelsheikh governorate. Atotal of 450 tissue samples involving liver, kidney, spleen, intestine from both fish species and gills from O. niloticus. Isolation and identification of the bacterial pathogens by traditional methods then antibiotic sensitivity test and resistance gene were detected. 23 isolates were obtained and distribution of Edwardesiella spp. among examined organs indicated that 9/100 (9%) isolates were detected from spleen, 6/100 (6%) from liver, 5/100 (5%) from intestine, 2/100 (2%) from kidney and 1/50 (2%) from gills. The predominant species were E. tarda so, 8 isolates were tested for 13antibiotic agents. The resistance were recorded in all 8 strains for Amoxicillin and Flumox, in 7 from 8 strains for Ampicillin, 6 from 8 for Cefotaxime, in 2 from 8 for Oxytetracycline and Streptomycin . Resistance profile genotypically in 3 isolates for β-lactamases( blaTEM, blaCTX) aminoglycosides (aada1)and tetracyclines (tetA(A))genes were 100% in all isolates. In conclusion presence of antibacterial resistance indicates misuse of antibacterial agents and affect on public health.