OBJECTIVE： To study the effects of total flavonoids of Drynariae rhizoma on the expression of HIF-1α and VEGF in synovial tissues and cartilage tissues/cells of knee osteoarthritis （KOA） model rabbits. METHODS： Totally 30 rabbits were randomly divided into normal group， model group and total flavonoids of D. rhizoma low-dose， medium-dose and high-dose groups （30， 60， 100 mg/kg）， with 6 rabbits in each group. Except for normal group， KOA model of rabbits was induced in other groups by cutting the left knee joint， shearing off the medial collateral ligament， anterior and posterior cruciate ligaments， and completely removing the medial meniscus. Five weeks after surgery， administration groups were given relevant dose of total flavonoids of D. rhizoma intragastrically； normal group and model group were given constant volume of normal saline intragastrically， 3 times a day， for consecutive 14 d. After last medication， the contents of HIF-1α and VEGF in synovial tissues of rabbits were detected by ELISA， and the relationship of them was investigated. HE staining was used to observe the morphology of the synovial tissues； immunohistochemical staining was used to detect the positive expression of HIF-1α and VEGF in cartilage tissues； protein expression of HIF-1α and VEGF in cartilage cells was detected by Western blot method. RESULTS： Compared with normal group， the contents of HIF-1α and VEGF in synovial tissues of rabbits in model group were increased significantly， with statistical significance （P＜0.01）； synovial tissues surface appeared fissures， and the cell layers were not clear and arranged in disorder； the number of positive cells of HIF-1α and VEGF in cartilage tissues was increased， and the relative expression of HIF-1α and VEGF in cartilage cells was increased significantly， with statistical significance （P＜0.01）. Compared with model group， the contents of HIF-1α and VEGF in synovial tissues of rabbits were decreased significantly in total flavonoids of D. rhizoma groups， with statistical significance （P＜0.05 or P＜0.01）， showing positive relationship （r＝0.923，P＜0.01）； the fissures were reduced， and the cell arrangement was more uniform， the degree of synovium injury was reduced； the number of positive cells of HIF-1α and VEGF in cartilage tissues was decreased， and the relative expression of HIF-1α and VEGF in cartilage cells was decreased significantly， with statistical significance （P＜0.05 or P＜0.01）. CONCLUSIONS： Total flavonoids of D. rhizoma can relieve synovium and cartilage injury in KOA model rabbits， the effect of which may be associated with regulating the expression of HIF-1α and VEGF in synovial tissues and cartilage tissues/cells.