Study DesignTranslational rodent study.ObjectivesTo investigate (1) chemokine-mediated mesenchymal stem cell mobilization and homing to the intervertebral disc and (2) using this technique to mitigate intervertebral disc degeneration in a rat model.Methods(1) Recruitment of mesenchymal stem cells (MSCs) to intervertebral discs (IVD) was investigated using intradiscal chemokines. Hydrogel containing SDF-1, RANTES, MCP-1, or empty control was injected intradiscally, followed by near-infrared (NIR) imaging to observe MSC localization. (2) A rat IVD degeneration model was induced by annular puncture. Intradiscal RANTES injection and/or systemic AMD3100 injection was performed. Longitudinal imaging and histological analyses including Rutges Score (histologic degeneration) assessed IVD degeneration mitigation post-treatment up to 12-weeks. Statistical analyses included ANOVA and mixed-effects models to evaluate recruitment, retention, and regenerative potential of MSCs.Results(1) 24 rats were included in the investigation of MSC recruitment. In vivo NIR signal on 1-day post-intervention was highest with RANTES ( < .05). Ex vivo NIR signal at 14-days post-intervention was highest with RANTES ( < .05). (2) 36 IVD degeneration model rats underwent intradiscal RANTES and/or AMD3100 injection. AMD3100-treated groups showed larger nucleus pulposus (NP) volumes and reduced histologic damage, with lower Total Rutges scores ( = .004). RANTES treatment alone reduced Total Rutges scores ( = .009) and protected against IVD height loss at 6 weeks.ConclusionsIntradiscal delivery of RANTES/CCL5 promotes a sustained and targeted recruitment of MSCs to the IVD. In a rat model of IVD degeneration, administration of systemic AMD3100 and intradiscal RANTES mitigates IVD degeneration.