Purpose: To evaluate the anti-inflammatory properties of Drynariae rhizome (Polypodiaceae) extract (DRE) on lipopolysaccharide RAW264.7 macrophage cells and its protective effects on interleukin (IL)-1 beta-stimulated SW1353 chondrocyte cells.Methods: The anti-inflammatory effect of DRE (12.5, 25, 50, and 100 mu g/mL) were measured by 5-lipooxygenase (LO) and cyclooxygenase (COX)-2 enzyme inhibitory activities, nitric oxide (NO) production in LPS-stimulated RAW264.7 cells using Griess reagent assay. Prostaglandins (PGE(2)) and leukotriene (LTB4) production were measured using enzyme-linked immunosorbent assay (ELISA). To investigate the protective effect on chondrocytes, the level of matrix metalloproteinases (MMP)-3,-9, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 was determined using zymography assay and ELISA kit in SW1353 cells stimulated with IL-1 beta.Results: Drynariae rhizome (Polypodiaceae) extract (DRE) had a significant (p < 0.05) inhibitory effect on 5-LO and COX-2 enzymes in a concentration-dependent manner compared to untreated group. In RAW264.7 cells, levels of NO, PGE(2) and LTB4 of DRE group were significantly (p < 0.05) decreased in study group (treated with DRE) at 12.5 mu g/mL compared to the group treated with LPS (100 ng/mL) alone. Additionally, in SW1353 human chondrocytes stimulated with IL-1 beta, MMP-3 and MMP-9 were significantly (p < 0.05) suppressed in DRE-treated group compared to IL-1 beta group alone, with no significant impact on TIMP-1 production.Conclusion: Drynariae rhizome (Polypodiaceae) extract (DRE) possesses anti-inflammatory and cartilage protection effects. It therefore has the potential to be developed as an effective natural pharmaceutical agent for inflammation or osteoarthritis.