Cartilage has a limited capacity to heal. Previously, we have shown that overexpression of Sox11 in rMSCs (Rat Mesenchymal Stem Cells) by lentivirus-mediated gene transfer leads to enhanced tri-lineage differentiation and accelerated bone formation in fracture model of rats. We observed that the fracture repair in the rats that received Sox11-modified rMSCs injection proceeded through an endochondral ossification process much faster than those in the control groups. However, the detailed role of Sox11 in rMSCs chondrogenic differentiation, as well as cartilage defect, is still not clearly clarified. Therefore, this study tests the hypothesis that Sox11 promotes chondrogenesis and cartilage defect repair by regulating beta-catenin. Sox11 was transduced into rMSCs using lentiviruses. The expression levels of beta-catenin and its downstream genes were evaluated by quantitative RT-PCR. The transcriptional activation of beta-catenin was proved by dual-luciferase reporter assay and co-immunoprecipitation was performed to evaluate Sox11-beta-catenin interaction. In addition, a cartilage defect model in SD rats was used to evaluate the cartilage regeneration ability of Sox11-modified rMSCs in vivo. We found that Sox11 transcriptionally activated beta-catenin expression and discovered the core promoter region (from -242 to -1414) of beta-catenin gene for Sox11 binding. In addition, Sox11 might regulate beta-catenin at the post-transcriptional level by protein-protein interaction. Finally, using a cartilage defect model in rats, we found Sox11-modified rMSCs could improve cartilage regeneration. Taken together, our study shows that Sox11 is an important regulator of chondrogenesis and Sox11-modified rMSCs may have clinical implication for accelerating cartilage defect healing.