Escherichia coli O ₁₅₇:H₇ causes outbreaks of diarrhea and hemolytic uremic syndrome which can cause acute kidney failure in human. Cattle are identified as the primary source of infection. In this study, the isolation of Escherichia coli O₁₅₇: H₇ was occurred through out of 100 milk samples from different localities in Egypt. The positive E.coli isolated was 45 from samples then serological identification was done to identify the serotypes of E.coli which revealed that only one sample donated to E.coli O₁₅₇: H_7.This only positive sample used for infection of rabbit models, which was used to evaluate the pathogenesis of E.coli O₁₅₇: _H7.The 10 rabbits were divided into: control group (3 rabbits) and experimental group (7 rabbits). Rabbits were inoculated by feeding tube with 10⁹ cfu of E.coliO₁₅₇: H₇.Fecal samples were collected from animals on days 2, 4, 6 post inoculation to determine the shedding of the pathogen. On day 13 after inoculation, intestine, kidney and liver were collected from slaughtered animals for histopathologic examination. The intestine showed necrosis and desquamation of epithelial lining with hyperplasia and neutrophilic infiltration. Kidneys showed microthrombosis in glomeruli and hyaline casts in the lumen of renal tubules. Liver showed severe congestion with sharp vacuoles in the cytoplasm of hepatocytes giving the cell the signet ring appearance.