Proinflammatory mediators such as prostaglandins (PGs), nitric oxide (NO), certain inflammatory cytokines and chemokines play a pivotal role in tumor development. The anti-inflammatory properties of naturally occurring phytochemicals are associated with significant reduction in the risk of certain cancers in vitro and in vivo. In the present study, we investigated the effects of soybean saponins on the production of proinflammatory mediators in LPS-stimulated peritoneal macrophages. Soybean saponins significantly inhibited the release of PGE(2), NO, TNFalpha and monocyte chemotactic protein-1 (MCP-1) in a dose-dependent manner. Soybean saponins also down-regulated the expression of COX-2 and iNOS at mRNA/protein levels. Moreover, soybean saponins suppressed NF-kappaB activation by blocking IkappaB-alpha degradation. Our data indicate that soybean saponins exhibit anti-inflammatory properties by suppressing the transcription of inflammatory cytokine genes through the NF-kappaB signaling pathway. The anti-inflammatory properties of soybean saponins may be useful for ameliorating inflammatory diseases as well as suppressing tumor progression.