The present study was designed for the development of a vaccine composed of different antigens (LPS, OMP, LPS+OMP and Bacterin) of avian pathogenic E. coli O78 to protect of chicken against colibacillosis. A total of 100 clinical samples from ill broiler chicks with colibacillosis were collected from different regions of AL-Qadisiya province. All subjected to isolation, identification, biotyping, serotyping and antimicrobial agent sensitivity for APEC by using biochemical, Api – 20E, and biotyping using patterns of different fermentation and sertyping by monospecific antisera for O and H antigen. The study showed that the prevalence of resistant APEC O78 isolates is very high. Of a battery of antibiotics used, these isolates were sensitive for only few antibiotics; Colistin sulphate and Gentamycin. The study have carried out in two stages; first stage included cultivation of identified isolates, extraction and purification of target antigens, and analysis for carbohydrate and protein contents. In addition, gel filtration and SDS-PAGE were performed for extraction of antigens; i.e. LPS. Second stage included the field trial, where 300 of 1 day aged broiler chicks were divided into 6 equal groups. Four of five challenged groups (inoculated with 1x10 9 cells/ml) were immunized with LPS (2.5 mcg/bird, sc) and OMP (2 mcg/bird, sc). The first initial dose was given at 5th day old of broiler chicks followed by a booster dose after 9 days. A clinical follow-up, morbidity and mortality were monitored daily. The challenge dose was given at 29 days old for all of studied groups. At 33rd day old, histopathological examination of different vital organs, CFU/g, cytokins assay for selected interleukins (IL-1B, IL-6, and TNF-α;TLiA) and immunoglobulines (IgG and IgM) assessment were performed. Mortality rate was significantly lower than that of positive control (56.7%) after bacterial challenge. Significant difference in IgG concentration was shown among groups. It was higher in vaccinated groups compared with positive control. Serum IL-6, IL-1B, and TNF-α concentrations were significantly higher in the 1st vaccinated group and placebo controls compared with positive group. Infected chicks showed gross lesions represented by airsaculitis, pericarditis and hepatitis, whereas, vaccinated groups appeared no significant gross lesions in air sacs, heart and liver. It is concluded that LPS and OMP of avian pathogenic E. coli O78 can protect chicken against colibacillosis.