Curcumin (1, 7-bis (4-hydroxyl-3-methoxyphenyl)-1, 6 heptadiene-3, 5-dione) is a potent natural anti oxidant and anti-inflammatory agent, which mediates its effects mainly by inhibiting the activity of enzymes like cyclooxygenase, lipooxygenases and phospholipase A2. Here we examined the possibility of curcumin affecting the production of matrix metalloproteinases (MMPs) by peripheral blood mononuclear cells (PBMCs), which play an important role in inflammation. Zymographic analysis and ELISA showed that curcumin significantly inhibited the activity and level of MMPs produced by PBMCs isolated from human and inflammation-induced rabbit in a concentration dependent manner. The administration of curcumin to inflammation-induced rabbits also caused downregulation of MMP-9. Kinetic analysis showed that the effect of curcumin was a delayed one indicating inhibition of de novo protein synthesis. RT-PCR and immunoblot analysis showed inhibition of the production of MMP-9 mRNA and protein respectively by human PBMCs, which were activated in vitro by Artocarpus Lakoocha agglutinin (ALA) lectin. EMSA and super shift showed activation of classical NFκB in in vitro activated PBMCs and treatment with curcumin inhibited activation of NFκB. Immunoblot analysis suggested that ALA-induced activation of NFκB leading to the upregulation of MMP-9 was due to the degradation of IκB-α. Curcumin inhibited the degradation of IκB-α, which inhibited the ALA mediated activation of NFκB and upregulation of MMP-9. These results indicated that anti-inflammatory effect of curcumin also involves inhibition of the production of MMP-9 in PBMCs.