Ankle osteoarthritis (OA) is an inflammatory deterioration chronic disease; yet, OA pathogenesis is obscure. There is no absolute cure from OA and the present pharmacological medication options are constrained and associated with adverse aspect effects. Clinically, Platelet-rich plasma (PRP) is usually used to cure OA. The present study was designed to evaluate the role of PRP in the treatment of experimentally Monosodium iodoacetate (MIA)-induced ankle osteoarthritis in the rat model. Thirty male Wistar rats were divided into three groups (each of 10 rats). Rats of group I were injected with 1 mg MIA in the right ankle joint for two consecutive days, while those of group II were treated with saline instead of MIA; and group III (osteoarthritic +PRP) rats were injected with PRP in the ankle joint at 14, 21, and 28 days after MIA injection. Paw oedema, scoring of arthritis, Matrix metalloproteinase 13 (MMP13) level, antioxidant response element (ARE) level, and joint transforming growth factor beta1 (TGF β 1) were evaluated. PRP reduces expression of joint, MMP13, ARE level, and TGF β 1. PRP also significantly reduces the score of arthritis. The administration of PRP decreases paw oedema in MIA-induced OA rats. These results suggest that PRP has marked effect against OA in MIA-induced osteoarthritic rats which are mediated through the anti-inflammatory and antioxidant effects.