As a common disease, osteonecrosis attracts more and more attention. In this paper, we investigated the relationship between the alterations of endothelial-derived and platelet-derived microparticles and the changes of coagulation and inflammation in the steroid-induced avascular osteonecrosis of femoral head using the rabbit model. We also explored the possible mechanism of the membrane particles associated with the development of the rabbit femoral head ischemic necrosis. With a 28-day continuous observation, the level of membrane microparticles was significantly heightened after methylprednisolone treatment. The coagulating and inflammatory factors also tended to increase. The data demonstrated that the levels of membrane microparticles had significantly individual differences, which meant the increased levels of membrane microparticles may be related to hypercoagulability, thrombosis, and inflammation in microcirculation and played an important role in steroid-induced osteonecrosis. It will be very useful and helpful to guide clinical trials.