Aim To investigate the antiproliferative mechanisms of probucol in rat vascular smooth muscle cells(VSMC) stimulated by H₂O₂. Methods Effects of probucol on cell cycle,DNA synthesis,cell proliferation and apoptosis in the presence of H₂O₂ were observed by means of MTT test,cell number count,3 H-TdR incorporation,FCM and RT-PCR. Results Probucol significantly inhibited proliferation and DNA synthesis of VSMC stimulated by H₂O₂.Cell number,A value and 3 H-TdR incorporation in probucol+H₂O₂ group were reduced by 46.9%,45.0%,and 39.5%,respectively,compared with H₂O₂ group(p<0.05).Probucol protected against H₂O₂-induced VSMC proliferation through inducing cell growth arrest at G0/G1 phase.H₂O₂ increased extracellular signal-regulated kinase-1(ERK-1) mRNA transcriptional levels by about 6 times and decreased mitogen-activated protein kinases phosphatase-1(MKP-1) mRNA by 82.2%,respectively,compared with controls.Probucol down-regulated the increase in H₂O₂-stimulated ERK-1 mRNA level and up-regulated MKP-1 mRNA level decreased by H₂O₂.Probucol induced apoptosis of VSMC under H₂O₂-stimulated condition. Conclusion Probucol suppresses H₂O₂-stimulated VSMC proliferation by inhibition of cell cycle progression via down-regulating ERK-1 mRNA transcriptional level,as well as inducton of apoptosis of VSMC.