The present research was carried out to determine the effects of a nuclear factor-kappaB (NF-kB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), derivative of the antibiotic epoxyquinomicin C, on normal human chondrocytes treated with interleukin-1b (IL-1b). This is a cell model particularly useful to reproduce the mechanisms involved in degenerative arthropathies, where oxidative-inflammatory stress determines a progressive destruction of the articular cartilaginous tissue. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inter-cellular adhesion molecule (ICAM)-1 was evaluated through Western blot analysis. The release of chemokines like monocyte chemoattractant protein-1 (MCP-1), regulated upon normal activation T-cell expressed and secreted (RANTES), and interleukin-8 (IL-8) were determined by ELISA assays. DHMEQ acts as a potent inhibitor of iNOS and COX-2 gene expression while also suppressing the production of nitrite in human chondrocytes. In addition, DHMEQ induces a significant dose-dependent decrease in ICAM-1 expression, MCP-1, RANTES, and IL-8 release. DHMEQ helps to decrease the expression and production of pro-in?ammatory mediators in IL-1b-induced chondrocytes. In conclusion, this study gives some new insight into the mechanisms of the anti-inflammatory effects of DHMEQ, which may become a therapeutic agent for treatment of chondro-degenerative diseases.