Ubiquitin is a protein that targets proteins for non-lysosomal degradation. It has been found to be present in a number of inclusions characteristic of neurodegenerative diseases. Using the fluid percussion model of closed head injury in the cat, a well-established model of diffuse axonal injury (DAI), we now report that the reactive axonal swellings and the retraction balls produced in this model stain positively with anti-ubiquitin immunohistochemistry. Furthermore, the affected axons become ubiquitin positive quickly (within the first 6 h after injury). Anti-ubiquitin immunohistochemistry compares well with the recently reported ability of antibodies to low molecular weight neurofilament proteins to demonstrate reactive axonal change in DAI, and it could provide additional clues to the pathogenesis of axonal transection.