This study describes the sequential histopathological changes that occur in the development of pressure ulcers experimentally induced in the fuzzy rat model. Computer-controlled pressure was applied for six hours at a maximum of five sessions, to skin over the greater trochanter of anesthetized rats. Lesions were similar, but more pronounced after the third, fourth, and fifth sessions as compared to the first or second sessions. Lesions developed first in the muscle rather than the dermis or epidermis. The lesion most often associated with pressure was necrosis of the panniculus carnosus muscle, often accompanied by damage to underlying adipose tissue. Recurrent pressure results in increasingly severe damage to the vascular system and parenchyma, consistent with an ischemia/reperfusion insult initiated through a free radical mechanism.