It was found in our previous study that oxidative modification LDL (Ox-LDL) could stimulate the proliferation of cultured human arterial smooth muscle cells (SMC). Yet, the mechanism responsible for the SMC proliferation induced by Ox-LDL is not clear. Proliferating cell nuclear antiger (PCNA), P53 and P27 are the key regulatory factors of cell replication. In order to observe the effects of Ox-LDL on cell cycling phase and PCNA, P53, P27 and c-erb B-2 expression in SMC, we used the flow cytometric method in the present study on the proliferation of cultured human SMC induced by Ox-LDL. The results showed a relation between the Ox-LDL mediated SMC proliferation and the cycling phase shifting. The relative number of S phase cells in the Ox-LDL group was higher than that of the control group (22.9% vs 15.7%). Ox-LDL mediated SMC proliferation was accompanied with the increasing expression of PCNA. The percentage of specific PCNA positive FITC cells in the Ox-LDL group was significantly higher than that of the control group (12.6% vs 6.5%). PMA, an activitor of protein kinase C (PKC), stimulated SMC proliferation and increased the PCNA exression in cultured SMC, while the PKC inhibitor, F109203X, significantly decreased the PCNA expression in SMC (PCNA positive cells 13.4% vs 0.4%). No changes were observed in the expression of P53, P27 and c-erb B-2 in the cultured proliferating SMC induced by Ox-LDL. In all, the results suggest that the OX-LDL mediated SMC proliferation is related to increasing S Phase Cells and involved in the PCNA expression which might undergo the PKC cellular signal transduction pathway.