Although some previous studies have reported patients who developed compartment syndrome or died because of locally applied negative pressure, no detailed investigation of pathologic changes caused by negative pressure-induced injury has been reported in the literature. The main purpose of this study was to examine the morphologic characteristics of injury caused by local negative pressure and correlate these with systemic changes. A total of 30 male Wister rats were used. Animals were randomly assigned to 6 groups. Negative pressure was applied to the right hindlimb of each animal in each group for periods of 0 (sham-operated), 30, 60, 90, 120, or 180 min using a vacuum pump. Macroscopic and microscopic changes induced by local negative pressure were already observed after 30 min and were exacerbated with time. The proportion of muscle degeneration was highest in the deep tissues, irrespective of exposure time. The observed increase in the weight of the injured hindlimb at 180 min was caused by an approximately 30% fluid shift to the hindlimb, demonstrating that the application of negative pressure to the hindlimb of rats can induce hypovolemic shock. We here reveal the morphologic changes induced by local negative pressure and discuss possible mechanisms of negative pressure-induced injury. (C) 2011 Elsevier Ireland Ltd. All rights reserved.