To investigate effect of cartilage morphology and CTX-Ⅱ,COMP and MMP-3 in serum on varying degrees of knee osteoarthritis in rats treated with Tongluozhitong herbal with low-frequency ultrasound transdermal penetration and explain the mechanism and advantage of the therapy.Methods: The rat models of KOA were built by the classic method of cutting off anterior cruciate ligament.SD rats were randomly divided into three groups: control group,the group of ultrasonic transdermal penetration and herbal topical groups.Left knees of rats were models.The control group were normally fed,and were randomly selected to extract serum and detect cytokines at 2nd/4th/8th weeks after surgery and the control group were observed on femoral condylar cartilage morphology and were evaluated by cartilage Mankin's score.Ultrasonic transdermal penetration group and herbal topical group were randomly selected for intervention treatment at the2nd/4th/8th weeks after surgery,1/d,30min,2 weeks.After 2 weeks,the data was recorded which was the same as the control group.Results: Cartilage morphology of the control group were changed significantly at 2nd/4th/8th weeks after modeling and cartilage Mankin's score was positively correlated with increased time and CTX-Ⅱ,COMP,MMP-3 in serum increased.Compared with the control group,cartilage morphology and Mankin's score at 2nd/4th weeks changed (P<0.05).Its role was better than topical medicine group:.Mankin's score decreased significantly at 2nd week(P<0.05).Compared with the control group,CTX-Ⅱof ultrasonic transdermal penetration group decreased sharply at 2nd/4th/8th weeks (P<0.05),and it was significantly better than herbal topical groups.Compared with the control group,COMP of ultrasonic transdermal penetration group decreased sharply at 2nd and 4th weeks (P<0.05).Compared with the herbs topical group,COMP of ultrasonic transdermal penetration group decreased at 4th week (P<0.05).Compared with the control group,MMP-3 of ultrasonic transdermal penetration group decreased at 2nd/4th weeks and there was diversity(P<0.05).Compared with the herbs topical group,MMP-3 of ultrasonic transdermal penetration group decreased at 4 weeks (P<0.05).Conclusion: The low-frequency ultrasound transdermal Penetration Tongluozhitong herbs can effectively Preventing and slowing the Progression of the disease.It may be reducing cartilage matrix-associated cytokines CTX-Ⅱ,COMP and MMP-3 in serum,slowing the degeneration of cartilage matrix; but there is no obvious effect on cartilage of severe KOA.Compared with the traditional method of herbs topical,it has the advantages of rapid onset and efficacy.