Objective To investigate the effects of Yishen Jiangu Pills on the expressions of AMPK/Cyclin Y/CDK16 pathway and autophagy and apoptosis-related proteins in cartilage tissue of rats with knee osteoarthritis(KOA);To discuss its mechanism for the treatment of KOA.Methods Totally 60 2-month-old SD rats were selected and randomly divided into sham-operation group,model group,agonist group,and TCM low-,medium-and high-dosage groups,with 10 rats in each group.Except for the sham-operation group,each group underwent medial meniscectomy and cruciate ligamentotomy to establish the KOA rat model,and the corresponding interventions were given for 14 d.Lequesne MG score was used to evaluate rat behavior,morphology of cartilage tissue was observed by HE and Safranin O-fixed green staining,and Mankin score was performed,Western blot was performed to detect expression of AMPK/Cyclin Y/CDK16 pathway proteins and autophagy proteins such as ULK-1,Beclin-1,LC3B,p62 and apoptotic proteins such as Bcl-2,Bax,Caspase-3,Caspase-9 in cartilage tissue,and autophagosome were observed using transmission electron microscopy.Results Compared with the sham-operation group,Lequesne MG score significantly increased in the model group(P<0.01),there was a significant defect in the surface layer of cartilage,thinning of the cartilage layer,disordered arrangement and irregular morphology of chondrocytes,and a significant increase in Mankin score(P<0.01),the expressions of AMPK,Cyclin Y,CDK16,ULK1,Beclin-1,LC3BⅡ/Ⅰ and Bcl-2 protein in cartilage tissue decreased,while the expressions of p62,Bax,Caspase-3 and Caspase-9 protein increased(P<0.01).Compared with the model group,the Lequesne MG scores of rats in the agonist group and TCM high-dosage group were significantly decreased(P<0.01),the TCM high-dosage group showed smoother cartilage surface,more regular arrangement of chondrocytes,basic integrity of cartilage layer structure,weakened cartilage tissue proliferation,and significantly decreased Mankin score(P<0.01),the expressions of AMPK,Cyclin Y,CDK16,ULK1,Beclin-1,LC3BⅡ/Ⅰ and Bcl-2 protein in cartilage tissue of rats in the agonist group and TCM medium-and high-dosage groups significantly increased(P<0.05,P<0.01),while the expressions of p62,Bax,Caspase-3 and Caspase-9 protein significantly decreased(P<0.05,P<0.01).Conclusion Yishen Jiangu Pills may promote chondrocyte autophagy and inhibit cell apoptosis by activating the AMPK/Cyclin Y/CDK16 pathway in cartilage tissue of KOA model rats,thus reduce cartilage damage.