Summary :Danofloxacin is recent antibacterial agent belong to the fluoro- quinolone family and is active against Gram-ve enterobacteria species. Ceftiofur sodium is a third-generation cephalosporin against Gram-ve and Gram+ ve and anaerobic pathogens.E.coli infection in chickens has been in the last decade a major problem in poultryfarms all over the world.The present study was performed to investigate the effect of danofloxacin (5mg /kg b. wt in drinking water) or ceftiofur sodium (2mg/ kg b. wt s/c) for three successive days on treatment of infected chicks with E.coli as well as on haemogram and some biocΙ-Antibacterial activity in vitro:The present investigation showed that MIC of danofloxacin was 0.6 µg/ml against E.coli and MIC of ceftiofur sodium was 0.2 µg/ml against E.coli .Sensitivity of E.coli pathogenic strains of avian origin to commercial discs namely danofloxacin, ceftiofur sodium , enrofloxacin, gentamicin, oxytetracyclin, chloramphenicol, ciprofloxacin, suphonamide with trimethoprime were measured. The results revealII – Antibacterial activity in vivo:A total number of 120 one day old chicks were classified into 6 equal groups, each of 20 chicks1st group Non-infected non treated (Healthy control)2nd group Non-infected treated with danofloxacin (5mg /kg b. wt in drinking water) for three successive days3rd group Non-infected treated with ceftiofur sodium (2mg/ kg b. wt s/c) for three successive days4th group Infected non treated (Infected control )5th group Infected treated with treated with danofloxacin (5mg /kg b. wt in drinking water) for three successive days6th group Infected treated with ceftiofur sodium (2mg/ kg b. wt s/c) for three successive daysBlood samples were taken at the end of 1st day, 7th day and 14th post-treatment for haematological studies and another blood samples were collected to separate serum for investigation of some biochemical parameters.1-Clinical symptoms:Normal chicks (non-infected non treated) and also infected treated with danofloxacin or ceftiofur sodium were healthy, viable showing no clinical symptoms along the course of the experiment. whereas E.coli infected and non-medicated group displayed clinicAdministration of danofloxacin or ceftiofur sodium to E.coli infected broiler chicks improved disease symptoms and completely disappeared at 7th day post treatment.2- Mortality rate:The mortality rate was zero in the groups non infected medicated with danofloxacin or ceftiofur sodium and group non infected non treated.Experimental infection with E.coli evoked high mortality rate (25 %) whereas group infected with E.coli medicated with danofloxacin or ceftiofur sodium reduced the mortality rate to 5 %.3- Lesion scores:Non-infected chickens and treated with danofloxacin or ceftiofur sodium showed no gross pathological lesions. Most infected non-treated chickens revealed severe gross pathological lesions such as pericarditis, perihepatitis, air saculitis, and enteritis. 4- Body weight and body weight gain:The groups non-infected and treated with danofloxacin or ceftiofur sodium showed a significant increase in body weight. The groups infected with E.coli and non treated with danofloxacin or ceftiofur sodium evoked a significant decrease in the body weight.5-Effect on food consumption and feed conversion ratio:The group non-infected treated with danofloxacin or ceftiofur sodium showed an increase in food consumption and feed conversion ratio when compared with control group. The chickens experimentally infected with E.coli and non medicated showed a decrease inIII-Haematological picture:The groups non infected and treated with danofloxacin or ceftiofur sodium for three successive days revealed a significant decrease in erythrocyte count, haemoglobin concentration, packed cell volume with a significant increase in WBCs count all over the IV. Serum biochemical parameters:1- Liver enzymes:Groups non-infected treated with danofloxacin or ceftiofur sodium elicited a significant increase in AST, ALT, and ALP activities post treatment all over the experimental period. The groups infected with E.coli and non- medicated produced significant incr2-Total protein, albumin and globulin levels:The group non- infected treated with danofloxacin or ceftiofursodium showed a significant decrease in serum total protein and albumin levels with a significant increase in globulin levels post- infection all over the experimental period. Birds experimentally infected with E.coli and non- medicated evoked a significa3-Kidney function tests:Serum uric acid and creatinine levels were significantly increased as a result of treatment of normal chickens with danofloxacin or ceftiofur sodium. Infection of chickens with E.coli elicited a significant decrease in serum uric acid and creatinine levelElectrolytes:Danofloxacin or ceftiofur sodium administration to normal chicks displayed a significant decrease in Ca2+ level with a significant increase in ph2+ and Mg2+ levels. Chickens experimentally infected with E.coli and non- medicated showed a significant decreHistopathological findings:The liver section of the group non- infected treated with danofloxacin or ceftiofur sodium showed mild degenerative changes in the hepatic cells and the liver section of the group infected with E.coli non- treated showed severe degenerative changes and nu