In this study, we evaluated the effects of avocado soybean unsaponifiables (Glycirrhiza globra) on proinflammatory mediators in chondrocytes and monocyte/macrophage-like cells. Cells were activated with 20 ng/ml lipopolysaccharide (LPS) for 24 h and cell supernatants were analyzed for prostaglandin E2 (PGE2) and nitrite content. One set of cells was activated for 1 h with LPS (20 ng/ml) for both reverse-transcriptase polymerase chain reaction (RT-PCR) and real-time PCR analysis of tumor necrosis factor-alpha (TNF-a), interleukin-1-beta (IL-1b), cyclooxygenase-2 (Cox-2), and inducible nitric oxide synthase (iNOS) expression. One set of cells was activated for 24 h to analyze released PGE2 and nitrite levels in the cellular supernatant.Glycirrhiza globra reduced TNF-a, IL-1b, Cox-2, and iNOS. The suppression of Cox-2 and iNOS expression was significant reduced in PGE2 and nitrite, in the cellular supernatant. In this study, we demonstrate the effects of Glycirrhiza globra on the isolated bovine chondrocyte and the human monocyte/macrophage-like cells. These observations provide a scientific comprehensive map to reduce the pain of osteoarthritis.