Abstract: AIM: To investigate the mechanism of desferrioxamine (DFO) activity on extracellular matrix metalloproteinse inducer(EMMPRIN) expression in macrophages and foam cells. The roles of MAPK pathway, retinoid x receptors (RXR) and nuclear transcription factor peroxisome proliferator-activated receptor γ (PPARγ) in DFO activity were explored. METHODS: THP-1-derived macrophages and foam cells were pretreated with MAPK (p38, ERK1/2) inhibitors or RXR ligand. The cells were then stimulated with/without DFO for 24 h. EMMPRIN expression, PPARγ expression and the effect of DFO on MAPK phosphorylation were assayed by Western blot. RESULTS: p38 MAPK inhibitor and RXR ligand alone did not modulate EMMPRIN expression but significantly blocked DFO upregulation of EMMPRIN expression. DFO activated p38 MAPK but did not affect PPARγ expression. CONCLUSION: p38 MAPK is involved in iron chelation upregulation of EMMPRIN expression in macrophages and foam cells. RXR may mediate DFO activity.