We have investigated the localization and regulation of a putative extracellular chaperone, clusterin, in the rat spinal cord after lesion. In control animals, clusterin is expressed in motoneurons, in meningeal and ependymal cells, and in astrocytes mainly located beneath the pial surface. Beginning at day 2 after hemisection at segmental level C6, clusterin levels increase in GFAP-positive astrocytes within the lesioned segment. Three weeks after trauma, clusterin mRNA and protein are elevated in neurons close to the lesion site and in glial elements within scar tissue and within degenerating fiber tracts rostral and caudal to the lesion. This study provides evidence for a role of clusterin in the subacute and late phase of spinal cord injury.