Aim To study the inhibitory effect of oxidized low density lipoprotein (ox-LDL) on the expression of caveolin-1 in vascular smooth muscle cell (SMC) and its relation with extracellular-signal regulated kinases 1/2 (ERK1/2). Methods Western blot was performed to evaluate the effects of ox-LDL (50 mg/L) or ox-LDL (50 mg/L) and PD98059 (25 μmol/L) on expression of caveolin-1and ERK1/2 in vascular SMC in different times. Results Ox-LDL (50 mg/L) obviously decreased caveolin-1 expression, and significantly increased ERK1/2 phosphorylation activity. However, the activation of ERK1/2 blocked by PD98059 significantly promoted caveolin-1 expression. Conclusions Downregulation of caveolin-1 expression in foam cell derived from vascular smooth muscle cell is involved in ERK1/2 phosphorylation activity and its signaling pathway activated by ox-LDL.