Background : C-reactive protein (CRP) is one of the most important biomarker for cardiovascular diseases. Recent studies show that CRP regulates cell survival, differentiation, and hypoxia-induced apoptosis. However, there is no direct evidence whether CRP controls cell cycle. Therefore, we investigated that CRP would regulate cell cycle progression in cardiac myocyte. Methods : Human purified CRP was dialyzed in PBS severally and incubated on rat embryonic cardiac myocyte H9c2 cells (0.1 to 10 關g/ml) from 24h to 72h. Cell viability measured by MTT and caspase-3 activity assay, and flow cytometry analysis were performed to interpret cell cycle regulation. Immunoblot analysis was observed with antibodies against phospho-p53, p21, cdk2, cyclinA. Results : CRP (10 關g/ml) suppressed H9c2 cell cycle progression, whereas there was no evidence of apoptosis. CRP-treated H9c2 cells displayed increased cell cycle arrest in S phase. In addition, CRP increased p53 phosphorylation and p21, while CRP reduced the cdk2 and cyclinA which were known to be involved in S phase cell cycle progression. And CRP induced MAPK phosphorylation on H9C2 cell. In MAPK inhibitor assay, CRP-induced p53 phosphorylation was inhibited by JNK inhibitor (SP600125) and AKT inhibitor (LY294002). Conclusion : These results suggest that activation of p53 is involved in CRP-mediated H9c2 cell cycle arrest via JNK, AKT signaling pathway. This present work implicates a novel effect of CRP on cardiac myocyte survival in various cardiovascular diseases.