N. sativa seeds is the source of fixed oil, which contain fatty acids and thymoquinone. N. sativa fixed oil topically or orally is used traditionally for management of pain in back, joints, musculoskeletal organs and arthritis rheumatoid.The aim of this review article was to evaluate the potential effects of N. sativa fixed oil in pain and inflammation, especially in arthritis rheumatoid.All information was extracted from accessible and inaccessible sources (books, electronic sources, thesis and etc.).The results of our investigation showed N. sativa fixed oil, especially thymoquinone content had valuable anti-inflammatory and analgesic effects via different pathways. The efficacy of thymoquinone as potential treatment was confirmed in different animal model of arthritis and the clinical studies confirmed the oral (n = 4) and topical use (n = 1) of N. sativa fixed oil without adverse effects in patients suffering from arthritis rheumatoid.The larger multicenter clinical trials for comparing the efficacy of topical, oral administrations and current treatment may help to understand better the efficacy of valuable fixed oil.