Osteopontin is a noncollagenous extracellular matrix protein that is expressed in various tissues. Recent studies have shown the upregulation of osteopontin expression in the ischemic cortex after cerebral infarction. We demonstrate here the upregulation of osteopontin expression in the spinal cord after compression injury. Laboratory rats were used in a compression model of spinal cord injury (30-g load for 5 min). Northern blot analysis showed that osteopontin mRNA expression levels reached a peak 3 days after injury (sevenfold; p < 0.05). In situ hybridization demonstrated osteopontin mRNA expression in necrotic areas from 24 h, peaking 3 days after injury. Immunohistochemistry detected osteopontin protein immunoreactivity from 12 h, peaking at 3 days. The peak time and distribution of osteopontin protein expression were coincident with those of osteopontin mRNA expression. Osteopontin expression in our model preceded that shown in the previously reported cerebral infarction models. Osteopontin protein was found in the cytoplasm at 3 days and secreted into the extracellular matrix at 7 days. Triple immunolabeling showed that osteopontin was localized in activated microglia surrounded by astrocytes.