Aim To investigate whether platelet factor 4 （PF4） modulates the matrix metalloproteinase-9（MMP-9） expression of macrophages. Methods THP-1 monocytes were differentiated into monocyte-derived macrophages by phorbol 12-myristate 13-acetate （PMA）. After incubation with PF4 （0～200 μg/L）, the MMP-9 expression of macrophages was determined by reverse-transcription polymerase chain reaction （RT-PCR） and Western blot. To determine the role of toll-like receptor 4 （TLR4） in the regulation of MMP-9 expression, macrophages were pretreated with TLR4 blocker for 30 min, then incubated with PF4. Results Macrophages that were untreated showed a relatively low MMP-9 and TLR4 mRNA or protein levels treatment of macrophages with PF4 increased MMP-9 and TLR4 expression. However, the high levels of MMP-9 and TLR4 expression induced by PF4 were significantly attenuated in the presence of TLR4 blocker.Conclusions PF4 may up-regulate MMP-9 expression in macrophages via TLR4.