The prevalence of Aeromonas hydrophila infection, the causative agent of motile Aeromonas septicemia, was 47.3% among the diseased cultured tilapias. Oreochromis niloticus was the more sensitive species to MAS. MAS infected tilapia showed loss of balance, reduced growth, fins and tail rot, ulcer and enlargement of the abdomen. Internally, the organs were congested. The intraperitoneal route was more pathogenic than intramuscular one in the experimentally infected 0. niloticus. Microscopically different organs showed histopathological changes.Also, changes in serum biochemical parameters were recorded. The antibacterial activity of Oxytetracyclin (OTC) was evaluated both invitro and in vivo. OTC was the drug of choice for the control and prevention of MAS under laboratory and field conditions. Immunization of tilapia with formalin-killed whole culture vaccine through intraperitoneal route gave successful results.