ABSTRACT: The efficacy of flumequine in treatment of Clarias gariepinus, experimentally infected with Aeromanas hydrophila was studied. Firstly pathogenesity text for the isolated A. hydrophila was done on 20 acclimatized C. gariepinus with weight range of 100-150 g. The results showed that 11 C. gariepinus showed hemorrhage on the fins especially on the pectoral and caudal fin 24 hr post challenge. 48 hr post challenge, redness, swelling and color changes were found on the skin around the site of injection. A mortality rate of 35% was recorded within 72 hr after challenge. The efficacy study performed a 90 clinically healthy C. gariepinus divided into 4 groups, first group as non infected group (control –ve group), the other 3 groups experimentally infected with C. gariepinus by Intra-muscular injection of 0.2 ml/fish of 24 hr pure broth culture. The fish in the second group were left without any medication as infected non treated group (control +ve group).Fish in the third group exposed to 72 hr bath treatment with fleumequine In a concentration of 150 mg/l while the group 4 the fish treated with flumequine by intra-muscular injection at a dose of 25 mg/kg b. wt. The morbidity 8 Mortality records in the 10 day following therapy revealed that, the morbidity rate in group 1 (control –ve group) was zero, while in group 2 (control +ve) was 93.93%, in group 3 and group 4 were 73.33%.The mortality records were zero, 66.66%, 33.3% and 40% in groups 1, 2, 3, and 4 respectively. Tissue residue study revealed that, the highest flumequine concentration at 24 hr after the end of drug administration was present in skin either following the bath or intra-muscular application (13.22 ± 3.52 and 2.06 ± 0.53 µg /g respectively).The drug withdrawal time from skin was more than 12 days following the bath treatment; however was 8 days after intra-muscular injection. This withdrawal time was reduced to 8 days for muscles of treated fish either by bath or intra-muscular injection which means that flumequine can be used safely 12 days before marketing of fish with no human health hazards.