This study aimed to evaluate the efficacy of cefquinome in treatment and controlling of Escherichia coli experimentally infected broiler chickens, in addition of detection of its residues using High performance liquid chromatography (HPLC). In this study, 150 one-day old Cobb broiler chicks were used. On the 14th day chicks experimentally infected and divided into 3 equal groups (50 each); control group (G1) non-infected, non-treated, (G2) infected with E. coli O78 non treated, (G3) infected with E. coli O78, cefquinome treated. Cefquinome was administrated 5th day post infection, intramuscularly by a dose of (2 mg/ kg b w.t) for 3 consecutive days. Experimental E. coli infection in broilers induced weakness, loss of appetite, depression, cough and watery diarrhea in addition to a recorded mortality (30%) with reduction in growth performance, erythrogram, total proteins, albumin, antioxidants and haemagglutination inhibition (HI) titers. In addition, a significant increase in feed conversion rate (FCR), leukocytic count, liver enzymes, kidney functions, total globulins, malondialdehyde, nitric oxide and lysozyme activity. Treatment with cefquinome led to decreased mortality rate, improvement in clinical signs, growth performance and modulated most of these altered parameters. Cefquinome's residues was not detected in breast muscles 3rd day and liver and kidneys 7th days post treatment. Therefore, it's recommended that cefquinome is a good choice for controling colibacillosis.