To elucidate possible mechanisms of anti-angiogenic activity by curcumin, we performed cDNA microarray and found that curcumin modulated cell cycle related gene expression. For further confirmation, DNA contents and expression levels of cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors (CDKIs) were examined by FACS analysis and Western blotting, respectively. Curcumin was found to induce G0/G1 and/or G2/M phase cell cycle arrest, up-regulate CDKIs, p21WAF1/CIP1, p27KIP1, and p53, and slightly down-regulate cyclin B1 and cdc2 in ECV304 cells. However, expression level of other cyclins and CDKs were not changed by curcumin. We, therefore, conclude that the up-regulation of CDKIs by curcumin plays a critical role in the regulation of cell cycle distribution in these cells, which may have a major role in anti-angiogenic activity of curcumin.