The ethyl acetate fraction from the seeds of Swietenia macrophylla (SMEAF) was studied for antiinflammatory properties using lipopolysaccharide (LPS)induced BV2 microglia. SMEAF significantly attenuated the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase2 (COX2), tumour necrosis factora (TNFa) and interleukin6 (IL6). SMEAF inhibited nuclear translocation of nuclear factorkappa B (NF-kB) via the attenuation of IkBa phosphorylation. Moreover, SMEAF markedly suppressed phosphorylation of Akt, p38 Mitogenactivated protein kinase (MAPK) and Extracellular signalregulated kinase 1/2 (ERK1/2) in LPSinduced BV2 cells. Treatment with specific inhibitors for Akt, NF-kB, p38 and ERK1/2 resulted in the attenuation of iNOS and COX2 protein expression. These findings indicated that SMEAF possesses antiinflammatory activities in BV2 cells by modulating LPSinduced proinflammatory mediator production via the inhibition of Aktdependent NF-kB, p38 MAPK and ERK1/2 activation. These results further advocate the potential use of S. macrophylla as nutraceutical for the intervention of neurodegenerative and neuroinflammatory disorders.