Objective: To investigate the effects of Yishen Zhuyu Tongluo Decoction on chondrocyte pyroptosis and ferroptosis in knee osteoarthritis (KOA) rats. Method: Anterior cruciate ligament dissection (ACLT) was used to create a KOA model in SD rats. The successfully modeled rats were randomly divided into a model group, a celecoxib group, and a traditional Chinese medicine group. Each group received medication intervention on the second day of modeling, for a total of 8 weeks. HE and safranin O staining were used to observe the pathological changes of articular cartilage; ELISA detection of serum IL-1β, IL-18; Micro CT analysis of bone microstructure. RT-PCR detection of MMP13, NLRP3, ASC, Caspase-1, GSDMD, IL-1β, IL-18, ACSL-4, FTH-1, GPX-4, and COX-2. immunohistochemical detection of NLRP3, Caspase-1and COX-2. Result: Compared with the sham surgery group, the expression levels of NLRP3, ASC, Caspase-1, GSDMD, IL-1β and IL-18 in the cartilage tissue of the model group were increased, the expression levels of ACSL-4 and COX-2 of model group rats were significantly increased, while the expression levels of FTH-1 and GPX-4 were significantly decreased. Compared with the model group, the NLRP3, ASC, Caspase-1, GSDMD, IL-1β and IL-18 expression levels of rats in the traditional Chinese medicine group were decreased, the expression levels of ACSL-4 and COX-2 of rats in the traditional Chinese medicine group were decreased, while the expression levels of FTH-1 and GPX-4 were increased. Conclusion: Yishen Zhuyu Tongluo Decoction could treat KOA by inhibiting chondrocyte pyroptosis and ferroptosis in KOA rats, reducing the level of serum inflammatory factors, and improving bone microstructure.