Objective:To discuss the clinical efficacy of modified Zuoguiwan on postmenopausal osteoarthritis of knee (KOA) with deficiency of liver and kidney based on theory of syndrome differentiation and treatment of kidney, and its effect on endocrine hormone and cartilage metabolism.Method:One hundred and forty patients of KOA were randomly divided into control group (70 cases) and observation group (70 cases) by random number table. Patients in two group got glucosamine hydrochloride capsule for 12 weeks, 1 capsule/time, 2 times/day, and those with obvious pain was added celecoxib capsules for 4 weeks, 0.2 g/time, 1 time/day. The control group took Kang Zengsheng pills orally. patients in observation group was also added with modified Zuoguiwan for 12 weeks, 1 dose/day. Before and after treatment, pain level during activity and rest by visual simulation of pain (VAS) were scored. And visual scale of osteoarthritis index (WOMAC) of Western Ontario and McMaster University, knee osteoarthritis severity index (ISOA), deficiency of liver and kidney, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were scored. And levels of serum estradiol (E₂), follicle stimulating hormone (FSH), luteinizing hormone (LH), transforming growth factor-β (TGF-β), interleukin-1β (IL-1β), matrix metalloproteinase-3 (MMP-3) and tumor necrosis factor-α (TNF-α) were scored.Result:Scores of VAS during activity and rest in observation group were lower than those in control group (P<0.01). The total score of WOMAC, scores of pain, stiffness, joint function, deficiency of liver and kidney, SAS and SDS were all lower than those in control group (P<0.01). Total score of ISOA, symptoms and signs, maximum walking distance, daily life were lower than those in control group (P<0.01). Levels of E₂, FSH, LH, TNF-α, IL-1β and MMP-3 were lower than those in control group (P<0.01). Level of TGF-β was higher than that in control group (P<0.01). And total clinical effective rate in observation group was 89.23%(58/65), which was higher than 74.60%(47/63) in control group (χ²=4.793, P<0.05).Conclusion:Modified Zuoguiwan can obviously alleviate symptoms, improve joint function, regulate the level of endocrine hormone, relieve anxiety and depression, regulate the environment of cartilage metabolism, inhibit inflammatory reaction, and improve the patients' ability of daily life and clinical efficacy.