Experimental reproduction of avian cellulitis was conducted by subcutaneous inoculation of 25-day-old broiler chickens with a field isolate of serogroup O78 Escherichia coli. Development of the cellulitis lesion occurred as early as 24 h post-infection. Reproduction of cellulitis occurred in 98% of inoculated birds, and E. coli was isolated from > 75% of cellulitis lesions. In addition to cellulitis, other lesions, including pericarditis, airsacculitis, osteomyelitis, arthritis, and perihepatitis, occurred in > 80% of birds inoculated with E. coli. Bacteremia occurred as early as 6 h post-infection and dramatically declined by 5 days post-infection. Seventeen of 59 (29%) birds inoculated with E. coli developed a fatal infection between 1 and 6 days post-infection, and bacteria were isolated from lesions in 98% birds. In contrast, E. coli was not isolated from lesions in birds that survived until days 7-14 post-infection. Birds that survived with cellulitis and other lesions until day 14 post-infection had a significantly lower body weight compared with the control group. This avian model of cellulitis and other lesions will be useful for studying the development of vaccination strategies for E. coli in broilers.