A Total 135, 1-3 months aged rabbits were used for this study. Faecal swabs were aseptically collected from different rabbit farms in Assiut Governorate. Diarrhea, ruffled fur and depression were observed in 45 out of them, while the rest were apparently healthy and 8 rabbits were chosen to be the control. These samples were examined bacteriologically for determination of the occurrence and frequency ofStaph. aureus. Thirty three isolates from the diseased rabbits at percentage of (24.4%) were  positive for Staph. aureus. Experimental infection in 6-8 week-old rabbits via subcutaneous (S/C) injection of isolated Staph. aureus led to 75% mortality with post-mortem lesions similar to a great extent to those of natural infection. Reisolation of infecting organism from internal organs and intestinal tract of dead and slaughtered rabbits at the end of observation period were conducted. Histopathological examination of the affected tissue revealed signs of septicemia and suppuration in various organs.