In order to know the influence of whole sonicated S.aureus antigens (WSSAgs) on S.aureus septic arthritis, 15, white local rabbits, both sex, their weights ranged between 1.25-1.50 Kg ,were randomly divided into 3 equal groups and treated as follow:1-the 1ST group was immunized with 0.5 ml of WSSAgs (3.3mg/ml protein concentration), two doses,14 days interval, at 28 days post-immunized .skin test was done by used soluble sonicatated S. aureus antigens and at day 30,Ab titers was recorded ,then the Vt and 2nd groups were challenged with 0.5ml of bacterial suspension containing 1X1OCFU/ml ,intra -synovial. the 3 group was inoculated with 0.5 ml of sterile normal saline and served as control negative group. All animals were sacrificed at 30 days post- challenge, sample from knee joint were taken for bacterial isolation and pathological examination. The results showed that WSSAgs elicited both humoral and cellular immune responses against S.aureus infection .severe swelling of the knee joint was noticed in the 2 group as well as the animals unable to use their legs. heavy bacterial isolation from infected joints was recorded in the 2nd group with severe histopathological lesions in the infected joints characterized by suppurative inflammation of the perchondral area with inflammatory reaction, necrosis and erosion of the articular cartilage and these changes were extended to subchondral bone trabeculae and bone marrow lead to suppurative inflammaion and necrosis of the bone trabeculae .while there was no clinical signs and no bacterial isolation reported in immunized infected animals as well as no clear pathological changes t noticed in joints of immunized-infected animals.