Danofloxacin is a new fluoroquinolone antibacterial agent used in theveterinary field for prevention and treatment of respiratory diseases ofherbivores, swines and poultry. In poultry, danofloxacin is used for thecontrol of mycoplasmosis and colibacillosis affecting poultry industry that causes major economic losses.The in-vitro susceptibility of eight native strains of avian origin wasdetermined to danofloxacin and other five members of commonly usedquinolones.The efficacy of therapeutic doses of danofloxacin in chicks experimentally infected with Mycoplasma, E. coli and mixed infection of . both microorganisms comapred with tylosin, oxolinic acid and lincospectinrespectively was investigated.Special emphasis was drawn to study the drugs induced side effects that could be reflected on some liver and kidney functions and histopathological changes involving, trachea, lungs, liver and kidneys.A- Antibacterial activity in-vitro:The present study demonstrated that MICs of novel fluoroquinolones(danofloxacin, enrofloxacin and norfloxacin) were much lower than that of older quinolones (flumequine, oxolinic acid and nalidixic acid) against tested avian pathogens namely Salmonella, Arizona, Proteus, Pseudomonas, Staph.aureus, Staph. citrus, Strept. faecalis and E. coli.The sensitivity test is of a great value in recommendation of theeffective antibacterial agents. Our results revealed that the tested isolates