Background: Although serum amyloid A (SAA) is an established biomarker of coronary artery disease (CAD), its direct role in matrix degradation is obscure. This study investigated the effect of SAA on the expression of matrix metalloproteinase-10 (MMP-10) in endothelial cells. The effect of celecoxib on SAA-dependent MMP-10 expression and its possible mediator were also investigated. Methods and Results: From our time course microarray screening, SAA (20 μg/ml) was found to increase MMP-10 mRNA expression over time (4–48 h) in human endothelial cells. Quantitative real-time PCR confirmed this transcriptional induction. Correspondingly, secreted MMP-10 protein was also markedly induced by SAA treatment for 24 h in a dose-dependent manner. We further examined cyclooxygenase-2 (COX-2) and its major product, prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), as possible mediators of MMP-10 induction. Direct PGE<sub>2</sub> treatment could result in MMP-10 induction. Celecoxib, a selective COX-2 inhibitor, suppressed MMP-10 secretion induced by SAA. Conclusions: SAA induced MMP-10 expression and celecoxib prevented its induction. MMP-10 induction was at least partly mediated by PGE<sub>2</sub>.