Due to the side effects of current therapies for osteoarthritis one of the alternative medicine is using herbal medicine such as Nigella sativa L. We examined that alcoholic extract of Nigella sativa (AENS) has an anti-inflammatory activity. Cells were activated with 100 ng/ml lipopolysaccharide for 24 h and cell supernatants were analyzed for PGE2 and nitrite content. One set of cells was activated for 1 h with LPS (100 ng/ml) for both reverse-transcriptase PCR and real-time PCR analysis of TNF-a, IL-1b , COX-2, and iNOS expression. AENS also reduced TNF-α and IL-1b expression in LPS-activated THP-1 cells. The present study demonstrates that the anti-inflammatory activity of AENS is not restricted to synoviocytes, but also affects monocyte macrophage-like cells that serve as a prototype for macrophages in the synovial membrane. These observations provide a scientific rationale for the pain-reducing and anti-inflammatory effects of AENS observed in osteoarthritis patients.