Aim To investigate the effects and mechanisms of high glucose on the migration of vascular smooth muscle cells （VSMC）. Methods VSMC were isolated from rat arteriae aorta. The 3rd～5th VSMC were incubated with low glucose （5.5 mmol/L）, high glucose （25 mmol/L） or mannitol （5.5 mmol/L glucose＋19.5 mmol/L mannitol）. After 24 h, VSMC migration was assayed with modified Boyden chamber. The effects of high glucose on F-actin cytoskeleton were analysed by immunofluorescence technique. The gene expression of α-SMA, osteopontin （OPN）, MMP-2 and MMP-9 was determined by real time RT-PCR. Results The migration of VSMC was obviously increased when the cells were cultured with high glucose. Compared with the low glucose group, mRNA levels of MMP-2 and MMP-9 increased obviously in the high glucose group. Moreover, high glucose induced VSMC conversion from contractile phenotype to synthetic phenotype and led to the reorganization of cytoskeleton. Conclusion High glucose promotes the migration of VSMC via complex mechanisms, involved in regulating VSMC phenotype transformation, increasing MMP expression and reorganizing cytoskeleton.