Abstract: Objective To investigate the therapeutic effect of vacuum sealing drainage (VSD) for treatment of rat femur osteomyelitis and to provide an initial reference for its clinical application. Methods To prepare femur osteomyelitis model, Staphylococcus aureus was injected into the femoral bone marrow of rats. After the model was successfully established, the rats were divided into five groups including 1-day, 3-day, 5-day and 7-day VSD treatment groups and model group. The VSD treatment groups were treated with vacuum sealing drainage, and the model group were treated with ordinary dressing therapy. Finally, the therapeutic efficacy of VSD treatment on rat femur osteomyelitis was evaluated by gross observation, body temperature, and wound bacterial counts. Results In the process of modeling, the rats demonstrated significantly-increased body temperature, obviously-decreased body weight, listlessness, reduced diet, difficulty of lower limb movement, local redness and swelling, and infection. A week later, local wound started to excrete exudate and pus. After VSD treatment, the body temperature of the rats returned to normal, the wound did not have secretions. With the prolongation of treatment time, the number of bacteria in the wound dramatically decreased, the wound became dry with ruddy color, and the fresh granulation tissue grew well. Conclusions The model of femoral osteomyelitis induced by Staphylococcus aureus has been successfully prepared, the success rate of modeling reaches 90%. The treatment effect of VSD is very significant.