STUDY DESIGN: Rabbit model study. OBJECTIVE: To examine whether cartilaginous endplate (CEP) destruction leads to endplate and vertebral marrow signal changes (Modic changes, MCs) on MR images. METHODS: Sixteen adult rabbits were used in the study and underwent an anterolateral procedure to expose the L2-6 intervertebral discs. The L4/5, L3/4 and L2/3 discs underwent annulotomy, annulotomy and CEP curettage, or annulotomy and chemonucleolysis, respectively, while the L5/6 disc served as a shame control. MR imaging was performed preoperatively and at 1, 3, and 6 months postoperatively to evaluate the presence or absence of MCs. After the last imaging, animals were sacrificed for histological study, focusing on endplate pathologies and their associations with MCs. RESULTS: Among the 64 endplates that underwent CEP curettage or were exposed to chemonucleolysis, there were 6 (9.4%), 19 (29.7%), and 32 (50%) endplates with MCs at 1, 3 and 6 months, respectively. No MCs developed in the sham controls. Both surgical curettage and chymopapain injection successfully induced CEP destruction. Endplates with full layer CEP defects were most likely to develop MCs (59.6% vs 11.4%, CONCLUSIONS: CEP destruction, induced either by physical curettage or chemical lysis, can lead to long-lasting inflammation in the vertebral marrow and Modic-like signal changes on MR images. CEP destruction may be a root pathology underlying MCs.