Royal jelly (RJ) is a gelatinous substance that bees produce to feed bees and queen bees. It’s frequently sold as a dietary supplement to treat a variety of physical ailments and chronic diseases. While it has long been used in traditional medicine, its applications in Western medicine remain controversial. The inhibitory effect of royal jelly on osteoarthritis was investigated in primary cultured rat cartilage cells and monosodium-iodoacetate (MIA)-induced arthritis rat model 10-hydroxy-2-decenoic acid (10-HAD) is the main fatty acid present in RJ. Among the criteria for RJ quality analysis, 10-HAD content has been proposed as a freshness parameter. We investigated the effect of RJ on the improvement of osteoarthritis on SD rats and they were divided into five groups. In this study, we examined the effect of enzymatic royal jelly (ERJ) administration on osteoarthritis. To determine the antiinflammatory effects of RJ, tumor necrosis factor alpha (TNF-α) and Interleukin-6 (IL-6) expression were measured after lipopolysaccharide (LPS) activation in RAW 264.7 cells. In in vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats. As a results, ERJ showed that TNF-α and IL-6 levels were decreased by ERJ treatment in a dosedependent manner. In conclusion, ERJ extract was able to inhibit articular cartilage degeneration by preventing extracellular matrix degradation and cartilage cell damage. It was considered that ERJ extract may be a potential therapeutic treatment for degenerative osteoarthritis.