Objective To observe the effects of GuBi mixture on chondrocytes apoptosis, Bcl-2 associated apoptosis promoter(Bad), aspartic acid-specific cysteine proteolytic enzymes 3 and 9(caspase-3 and caspase-9), and nuclear transcription factor -κB(NF-κB) in KOA model mice. Methods KOA mouse model was prepared by Hulth method. After successful preparation of the model, KOA mouse were divided into three group,respectively used GuBii mixture、Osaminethacine dissolved in same volum of distilled water to full the stomach，and normal saline（NS） group used equal volum of NS to full the stomach,twice daily，continue 8weeks. The pathological changes of articular cartilage were observed by hematoxylin-Eosin(HE) staining. Immunohistochemistry(IHC) was used to detect the expression of Bad, Caspase-3, Caspase-9 and NF-κB proteins in articular cartilage.The expressions of Bad, Caspase-3, Caspase-9 and NF-κB mRNA in articular cartilage were detected by real-time fluorescence quantitative RT-PCR. Results In the saline group, cartilage defects were observed and the number of chondrocytes decreased significantly. Compared with the normal saline group, the cartilage tissue of GuBi mixture and Osaminethacine group was significantly improved, and the number of chondrocytes on the surface was increased. The expressions of Bad, Caspase-3, Caspase-9, NF-κB protein and mRNA on the cartilage surface in the saline group were all high.Compared with normal saline group, the expression of Bad, Caspase-3, Caspase-9, NF-κB protein and mRNA in GuBi group were decreased (P<0.05 or P<0.01). Conclusion By down-regulating the expression of Bad, Caspase-3, Caspase-9, NF-κB protein and genes on the surface of cartilage tissue, GuBi mixture can effectively inhibit the articular cartilage of KOA mice and delay the pathological process of articular cartilage degeneration.