Preceding the development of therapeutic strategies for spinal cord injury is an identification of those pathological processes that might serve as therapeutic targets. Although demyelination has been documented as a secondary degenerative component of spinal cord injury in several species including humans, the extent of demyelination and its functional consequence remain unknown. In this report, we document the extent of demyelination and remyelination up to 450 days following contusive spinal cord injury in adult rats. The overall number of demyelinated axons peaked at 1 day post injury, declined by 7–14 days post injury, and then progressively increased up to 450 days post injury. Oligodendrocyte and Schwann cell remyelinated axons appeared by 14 days post injury. Although remyelinated axons were present from 14 to 450 days post injury, remyelination was incomplete, as indicated by the presence of demyelinated axons at every time point examined. These studies demonstrate for the first time that spinal cord injury is accompanied by chronic progressive demyelination, and they substantiate demyelination as a target for therapeutic intervention. J. Comp. Neurol. 486:373–383, 2005. © 2005 Wiley-Liss, Inc.