Objective: An investigation into the mechanism by which extracorporeal shock wave therapy modulates the ERK1/2 signalling pathway to regulate autophagy in rabbit chondrocytes with knee osteoarthritis, using an animal model.Methods: Forty New Zealand White rabbits were randomly assigned using a pseudorandom number table to four groups: sham surgery, model, shock wave, and ERK1/2 signalling pathway inhibitor group, comprising ten rabbits each. Except for the sham surgery group, the other four groups underwent knee osteoarthritis (KOA) modelling using the modified Hulth method. Following modelling, the shock wave group received extracorporeal shock wave therapy once weekly for four weeks. The inhibitor group received intra-articular injections of the ERK1/2 signalling pathway inhibitor U0126 0.1mL（100 μmol/mL） prior to each shock wave session, once weekly for four weeks. The sham surgery and model groups were solely immobilised in restraints without any additional intervention. Tissue sampling was performed after 4 weeks of intervention. The modified Lequesne MG scale assessed behavioural changes before and after intervention in all groups; radiographs evaluated knee joint imaging changes; haematoxylin-eosin staining and Fuchsin-green staining examined cartilage histopathology; transmission electron microscopy detected chondrocyte autophagy; Real-time quantitative PCR measured ERK1/2, ULK1, and Beclin-1 mRNA expression in cartilage tissue across groups; Western Blot analysed P-ERK1/2, ERK1/2, ULK1, and Beclin-1 protein expression in cartilage tissue; Immunohistochemical staining examined the in situ expression and distribution of P-ERK1/2, ULK1, and Beclin-1 within cartilage tissue.Results:Compared with the sham-surgery group, rabbits in the model group exhibited lower behavioural scores, marked damage to joint radiographic structures, severe cartilage degeneration, a reduction in autophagosomes within chondrocytes, and significantly lower levels of P-ERK1/2 protein as well as mRNA and protein expression of the autophagy-related molecules ULK1 and Beclin1 in cartilage tissue (P<0.05). Compared with the model group, the ESWT group of KOA rabbits showed improvements in both behavioural scores and radiographic findings; the cartilage surface was relatively smooth, and the matrix staining was superior to that of the model group. There was an increase in autophagosomes within chondrocytes, and the mRNA and protein expression levels of P-ERK1/2, as well as the autophagy-related molecules ULK1 and Beclin1, were significantly elevated in the cartilage tissue (P<0.05). Compared with the ESWT group, the degree of behavioural and imaging improvement in the inhibitor group of KOA rabbits was weaker than that in the ESWT group; cartilage damage was exacerbated and the number of autophagosomes correspondingly decreased; the protein and mRNA expression levels of the relevant molecules were downregulated compared with the ESWT group (P<0.05).Conclusions: Extracorporeal shock wave therapy regulates autophagy in rabbit chondrocytes with knee osteoarthritis by modulating the ERK1/2 signalling pathway, thereby exerting a protective effect on articular cartilage and slowing the progression of knee osteoarthritis; this provides experimental evidence for the clinical application of this therapy.