In present study, we investigated the effects of aspirin on matrix metalloproteinase (MMP)-9 mRNA expression and release and its possible mechanisms in macrophages derived from THP-1 cells. The macrophages were divided into different groups and treated with different drugs, the mRNA expression of MMP-9, peroxisome proliferator-activated receptor (PPAR) ⍺ and γ, cyclooxygenase (COX)-2, membranebound prostaglandin E synthase (mPGES)-1 in macrophages were examined with reverse-transcription polymerase chain reaction, and the protein expressions of PPAR ⍺ and γ, mPGES-1 were detected by Western-blot, the levels of MMP-9 and PGE₂ in cultured supernatants were determined with enzyme-linked immunosorbent assay. The results indicated that after the macrophages were incubated with aspirin for 24h, the MMP-9 mRNA expression and release were decreased, while the PPAR ⍺/γ mRNA and protein expression was increased, respectively, and PPAR ⍺/γ agonists could also decrease MMP-9 mRNA expression and release. Additionally, the COX-2 mRNA expression, mPGES-1 mRNA and protein expression in macrophages were all decreased after incubation with aspirin for 24h and the PGE₂ release was also decreased. The macrophages stimulated with PGE₂ for 24h might increase the MMP-9 mRNA expression and release. When PGE₂ plus PPAR ⍺ agonist or PPAR γ agonist were simultaneously used, the stimulation of MMP-9 mRNA expression and release by PGE₂ was significantly decreased. It might be concluded that aspirin could inhibit the MMP-9 gene expression and release through the PPAR⍺/γ and COX-2/mPGES-1-mediated pathways and the two pathways might be partly overlapped and even be interrelated.