Aim To Investigate whether activate lymphocyte contact induces the expression of matrix metalloproteinases in vascular smooth muscle cells. Methods The healthy human peripheral blood lymphocytes, which were activated by incubating with PMA and then fixed in 1% paraformaldehyde, were incubated with cultured human fetal aortic vascular smooth muscle cells (hVSMC). The gelatinase (MMP-2 and MMP-9) and stromelysin (MMP-3) activity in conditioned culture media were demonstrated by gelatin SDS-PAGE and casein SDS-PAGE. Results Unstimulated cultured hVSMC constitutively express 72 kDa zymogen of MMP-2 (pro-MMP-2) with a little of 66 kDa activated MMP-2, and no MMP-1, MMP-3, MMP-9 were detected by SDS-PAGE. After incubating with PMA-stimulated lymphocytes for 24 hours, zymography showed the MMP-1, MMP-3 and MMP-9 activity in the conditioned culture media, and activated MMP-2 increased 198%±27% compared with the control group (p<0.01). The unstimulated lymphocytes had no effect on MMPs synthesis of human fetal aortic vascular smooth muscle cells and PMA-activated lymphocyte had no gelatinolytic and caseinolytic activity on its own. Conclusions Activated lymphocytes may play an important role in atherosclerotic plaque repture through inducing vascular smooth cells to produce increased MMP and activate MMP-2.