Object: The aim of this study was to compare transplanted mesenchymal stem cells (MSCs) with nucleus pulposus cells (NPCs) in a degenerative disc model in rabbits to determine the better candidate for disc cell therapy. Methods: Mesenchymal stem cells and NPCs were transplanted in a rabbit model of disc degeneration. Changes in disc height, according to plain radiography, T2-weighted signal intensity on MR imaging, histology, sulfated glycosaminoglycan (sGAG)/DNA, and associated gene expression levels, were evaluated among healthy controls without surgery, sham-operated animals in which only disc degeneration was induced, MSC-transplanted animals, and NPC-transplanted animals for a 16-week period. Results: Sixteen weeks after cell transplantation, in the MSC- and NPC-transplanted groups, the decline in the disc height index was reduced and T2-weighted signal intensity increased compared with the sham-operated group. Safranin O staining showed a high GAG content, which was also supported by sGAG/DNA assessment. Disc regeneration was also confirmed at the gene expression level using real-time polymerase chain reaction. However, no significant differences in expression were found between the NPC- and MSC-transplanted groups. Conclusions: Study data showed that MSC transplantation is effective for the treatment of disc degeneration and seems to be an ideal substitute for NPCs.