Objective To investigate the mechanism of cartilage injury and inflammation in the WHBE rabbit KOA model and the effect of platelet-rich fibrin releasates (PRFr) treatment on the KOA process, we established a WHBE rabbit KOA model by excision of medial collateral and partial patellar ligaments and administered a PRFr solution. Methods Twenty-four WHBE rabbits were randomly divided into three groups: normal control ( NC) group ( n= 6),model(KOA) group(n= 12), and cure(PRFr) group ( n= 6). KOA and PRFr groups were injected with 0. 5 mL saline and PRFr into both joint cavities on 7 and 14 postoperative days, respectively. At 4 and 8 weeks of modeling, the knee joint grade scoring, X-ray imaging, and gross scoring were performed. Serum levels of IL-1β, TNF-α, and MMP-13 were measured by ELISA. At 4 weeks, 6 animals in the KOA group were euthanized, and at 8 weeks, the remaining animals in each group were euthanized. Pathological sections were prepared after decalcification, and then HE, toluidine blue, and safranin O-fast green staining and immunohistochemical analysis of TGF-β, BMP3, and NF-κB were conducted. Results The Lequesne MG behavioral score, Mankin’ s score, and Pelletier score of WHBE rabbits after the operation were significantly increased compared with the NC group (P<0. 01). Pathological observations revealed surface defects of the cartilage and partial loss of chondrocytes. These result indicated that the KOA model was established successfully. In KOA rabbits, knee joint swelling, joint pain stimulation, and movement limitation were obvious. X-rays showed a high-density soft tissue shadow, indicating more joint effusion and a rough articular surface in general. After PRFr treatment, the serum levels of proinflammatory factors IL-1β, TNF-α, and MMP-13 in KOA model rabbits were significantly reversed (P<0. 05,P<0. 01). Additionally, the cartilage surface became smooth, and most chondrocytes were neatly distributed. Expression levels of TGF-β, BMP3, and NF-κB induced by KOA were also significantly decreased (P<0. 01). Conclusions We successfully established a KOA model in WHBE rabbits, and PRFr improved the cartilage injury and inflammation of the WHBE rabbit KOA model through TGF-β/ BMP and NF-κB pathways.