To investigate the effect of acupotomology intervention on the expression of ferroptosis-related proteins，i.e.，solute carrier family 7 member 11(SLC7A11)，glutathione peroxidase 4(GPX4)，and glutathione(GSH)，in chondrocytes of rabbits with knee osteoarthritis(KOA)，and to explore the mechanism of acupotomology therapy in inhibiting chondrocyte ferroptosis.Methods:Thirty-five rabbits were randomly divided into blank group，model group，model+inhibitor group，acupotomology group，and acupotomology+inhibitor group according to a random number table，with 7 rabbits in each group.Except for the blank group，all rabbits underwent left hind limb immobilization for 6 weeks to establish the KOA model.The acupotomology group and the acupotomology+inhibitor group received a 3-week intervention.Transmission electron microscopy was used to observe chondrocyte injury and mitochondrial ultrastructure.Western blot was used to detect SLC7A11 and GPX4 protein expression in chondrocytes，and biochemical methods were employed to assess GSH levels.Results:Compared with the blank group，the model group exhibited disrupted cell membranes，cytoplasmic vacuolization，swollen organelles，and damaged mitochondria with ruptured outer membranes，reduced or disappeared cristae.Expression of SLC7A11 and GPX4 proteins，as well as GSH levels，were significantly reduced(P<0.01).Compared with the model group，the acupotomology group showed relatively intact cell membranes，moderate number of organelles，and normalized mitochondrial morphology.SLC7A11 and GPX4 expression levels were significantly increased(P<0.01)，and GSH levels were also higher(P<0.05).Compared to their corresponding intervention groups，both the model+inhibitor group and acupotomology+inhibitor group showed significantly lower expression of SLC7A11 and GPX4(P<0.01)，and reduced GSH levels(P<0.05).Conclusion:Acupotomology intervention can upregulate the expression of SLC7A11，GPX4，and GSH in KOA model rabbits，suggesting that its inhibitory effect on chondrocyte ferroptosis may be achieved through modulation of the SLC7A11/GPX4 signaling pathway.