Ankle osteoarthritis (OA) is a long-standing inflammatory degeneration disease; until now, its pathogenesis remains ambiguous. There is no complete remedy from OA and the present pharmacological therapy choices are restrained and combined with undesirable side effects. Clinically, Hyaluronic acid (HA) is widely consumed to cure OA. The present experiment aimed to assess the role of HA in the remedy of experimentally Monosodium iodoacetate (MIA) -induced ankle OA in the rat model. Thirty male Wistar rats were divided into 3 groups (each of 10 rats). Rats of group I were injected with 1 mg MIA in the right ankle joint for two successive days, while those of group II were treated with saline instead of MIA; and group III( osteoarthritic + HA) rats were injected with HA in the ankle joint at 2nd, 3rd, and 4th weeks following injection of MIA. Bodyweight, ankle measurement, total leukocytes count (TLC), antioxidant response element (ARE) level, and joint Magnetic Resonance Imaging (MRI) were investigated. HA reduced expressions of joint ARE level. HA also markedly reduced the TLC. The administration of HA decreases ankle measurement in MIA-induced OA rats. MRI of HA showed a gradual reduction in joint damage. These results suggest that HA has improvement effects on OA rats which are assessed through anti-inflammatory and antioxidant effects.