Objective To explore a modeling method of the combination of disease and syndrome of knee osteoarthritis KOA based on the pathogenesis theory of “Deficiency, Stasis and Toxicity” in (KOA). Methods Overall, 24 New Zealand white rabbits were randomly divided into a SHAM group (n= 8), MODEL group (n= 8), and TCM + MODEL group (n= 8). The SHAM group was fed normally. The MODEL group was established by plaster fixation. In the TCM + MODEL group, we hydrocortisone gavage and TCM etiological factors (wind, cold, and wet) were combined based on plaster fixation. After 6 weeks of modeling, each group was comprehensively evaluated, including the TCM syndrome and sign score, knee imaging, articular surface gross observation, Saffron O?solid green staining, blood and articular fluid IL?6 and TNF?α levels, hemorheology, and serum CORT, T, SOD, and MDA levels. Results The TCM symptom and sign score, imaging score, gross observation score, Mankin score, levels of IL?6 and TNF?α in joint fluid, hemorheology indexes (PV and RCAI), and serum MDA in the TCM + MODEL group were significantly higher than those in SHAM and MODEL groups (P< 0.05). Compared with the MODEL group, serum CORT, T, and SOD were significantly decreased in the TCM + MODEL group (P< 0.05), while serum IL?6 and TNF?α were not significantly different (P> 0.05). Conclusions By plaster fixation combined with the model of kidney deficiency syndrome gavage with hydrocortisone and etiological treatment with traditional Chinese medicine, including wind, cold, and wet, we reproduced the combination of disease and syndrome model of KOA with the characteristics of “Deficiency, Stasis and Toxicity”, which provides an experimental basis for further research on syndrome differentiation and treatment of KOA by traditional Chinese medicine.