Objective To investigate the immunohistochemical localization of dermatan sulfate (DS) and its correlation with the fibrotic scar formation in the mouse brain after traumatic injury.Methods The nigrostiatal dopaminergic pathway was unilaterally transected in 10-weeks-old male ICR mice. The operated mice were sacrificed and the brains were obtained 1, 4, 7 and 14 days after injury. Immunohistochemical localization of DS was examined using the antibodies GD3A12 and LKN1 which specifically recognize DS subtypes. The fibrotic scar formation was evaluated by the fibronectin antibody and its correlation with DS localization was investigated by double immunofluorescent staining. Results In normal adult mice brains, the localization of GD3A12 and LNK1 immunoreactivity was in meninges and blood vessels of the brain surface. At the 4th day after injury, the first DS immunoreactions appeared in some cells at the edge of the lesion site and a dense deposition of DS immunoreactivity was in the central region of the lesion site where FN-immunoreactive fibroblast formed the fibrotic scar afterwards. Double immunofluorescent staining demonstrated that intense DS immunoreactivity was localized in the fibrotic scar of the lesion core and was almost completely overlapped well with FN immunoreactivity, but not with CD45-immunoreactive macrophages and glial fibrillary acidic protein (GFAP)-positive reactive astrocytes.Conclusion The localization of DS immunoreactivity after brain injury is confined in the fibroblast of the fibrotic scar, suggesting that DS may play some role in the formation of the fibrotic scar.