This study investigated the effects of fucoidan (extract from Hizikia fusiforme ) on symptoms and inflammatory cytokine activation in rats with monosodium iodoacetate (MIA)-induced osteoarthritis (OA). Forty male SD rats were divided into five groups, including normal, negative control (MIA), positive control (Lyprinol), and two experimental groups treated with 50 or 100 mg/kg fucoidan. Weight-bearing assessments were done after MIA injection into the right knee to induce OA. After 14 days of treatment, microcomputed tomographic (micro-CT) images were made of rat knee joints, and then animals were sacrificed for joint histology and inflammatory cytokine level assessments. MIA injection successfully induced OA by causing 40% weight-bearing imbalance, severe bone loss and cartilage degeneration, and markedly increased cytokine levels. However, fucoidan groups showed over 45% of imbalance and no articular cartilage surface lesions or change in subchondral trabecular bones in Micro-CT images. Histological analysis revealed that cartilage morphology and cell counts were also normal in the 100 mg/kg fucoidan group. In addition, the 100 mg/kg fucoidan groups exhibited lower serum tumor necrosis factor alpha (TNF- α ) (30%), interleukin 1 beta (IL-1 β ) (48%), and matrix metalloproteinase-1 (MMP-1) (65%) compared to the MIA groups. These results suggest that administration of fucoidan prevents the progression of OA in a MIA-induced OA rat model.