Mice display a wound healing process after spinal cord injury that has not been seen in any other species. Rather than exhibiting progressive necrosis and cavitation at the injury site, the mouse lesion site fills in with connective tissue. The connective tissue matrix then undergoes a remodeling in which it contracts, drawing the two ends of the injured spinal cord closer together. One possible explanation for this unique wound healing response is that the spinal cord is much smaller in mice than in rats or other species that have been analyzed. To evaluate this possibility, we compared the histopathological response to spinal cord injury in mice, hamsters (in which the spinal cord is similar in size to that in mice), and rats. Crush injuries were produced at T9, and lesion area and cavitation were assessed using quantitative morphometry at 1, 3, and 8 weeks post-injury. Both hamsters and rats exhibited large lesions and areas of cavitation that increased from 1 to 3 weeks and then stabilized. In mice, the lesion site contained compact meshworks of cells and connective tissue that decreased in size over time. In rats, the cavities contained substantial degeneration debris, whereas in hamsters, cavities were fluid-filled cysts with minimal debris. Hamsters had the largest lesions relative to the cross-sectional area of the spinal cord, despite having a spinal cord similar in size to the mouse. These results indicate that the physical size of the spinal cord does not determine the unique histopathological responses after spinal cord injury in mice.