Background: Osteoarthritis (OA) is the most common cause of joint pain, affecting approximately 15% of the population. Recent studies indicate that quadriceps muscle weakness is directly involved in the pathogenesis of OA-associated joint pain. Oxidative stress plays an important role in skeletal muscle dysfunction. Sesame oil is a natural product with excellent antioxidative property. However, whether sesame oil can decrease OA-induced joint pain has never been investigated. Objective: The aim of the present study was to examine the effect of sesame oil on OA-induced joint pain in rats. Design: OA-associated joint pain in rats was induced by medial meniscal transection in rats. Sesame oil (0, 1, 2, or 4 ml/kg/day, orally) was given to rats 7 days after OA induction, while the parameters were determined 7 days after sesame oil administration. Results: Daily sesame oil treatment for 7 days significantly decreased OA-associated joint pain. Sesame oil decreased muscular interleukin-6 and increased citrate synthase activity and myosin heavy chain IIa mRNA expression. Furthermore, sesame oil decreased muscular lipid peroxidation, nuclear Nrf2 protein expression, and reactive oxygen species generations as well as increased glutathione production and glutathione peroxidase activity in OA rats. Conclusions: Sesame oil may relieve OA-associated joint pain by inhibiting quadriceps muscular oxidative stress, at least partially, in rats.