Objective WHBE rabbit KOA model was established by excision of medial collateral and partial patellar ligaments and intervention with platelet-rich fibrin release solution (PRFr). To investigate the mechanism of cartilage injury and inflammation in WHBE rabbit KOA model and the effect of PRFr intervention on KOA process. Methods Twenty-four WHBE rabbits were randomly divided into three groups: normal control (NC) group (n=6), KOA group (n=12) and PRFr group (n=6). The KOA group and PRFr group injected 0.5 mL of saline and PRFr into both joint cavities on the 7th and 14th postoperative days, respectively. At 4 and 8 weeks of modeling, knee joint grade score, X-ray imaging observation and gross score were performed. Serum levels of IL-1β, TNF-α and MMP-13 were detected by ELISA. Pathological sections were made after decalcification, and then HE staining, toluidine blue staining, safranin o-fast green staining and immunohistochemical expression of TGF-β, BMP3 and NF-κB were detected. Results Lequesne MG behavioral score, Mankin's score and Pelletier score of WHBE rabbits after the operation were significantly increased vs NC group (P<0.01); Pathological observation shows surface defects of cartilage and partial loss of chondrocytes; These results above indicated that the KOA model was established successfully. In KOA rabbits, knee joint swelling, joint pain stimulation and movement limitation were obvious, and X-ray showed high-density soft tissue shadow, indicating more joint effusion, and rough articular surface in general. After PRFr treatment, the levels of serum inflammatory factors (IL-1β, TNF-α, MMP-13) in KOA model rabbits were significantly reversed (P<0.05, P<0.01), and the surface of cartilage became smooth, and most of the chondrocytes were neatly distributed. At the same time, the expression levels of TGF-β, BMP3 and NF-κB induced by KOA were significantly decreased(P<0.01). Conclusion This study successfully established the KOA model of WHBE rabbits, and PRFr can improve the cartilage injury and inflammation of WHBE rabbits KOA model through TGF-β/BMP and NF-κB pathways.