In the current study, we prepared eighty-five different kinds of solvent fractions of rice wine lees and nuruk extracts and investigated their effects on cell viability and nitric oxide (NO) production in mouse RAW 264.7 cells. Among the treated solvent fractions, only three solvent fractions (KSD-E1-3, KSD-E2-3 and KSD-E4-3) significantly decreased NO production in LPS-activated RAW 264.7 cells without affecting cell viability. And, they also reduced the expression of pro-inflammatory genes such as COX-2, TNF-alpha and iNOS. To understand the molecular mechanisms involved in the inhibition of inflammation in (KSD-E4-3)-treated RAW 264.7 cells, we carried out oligo DNA microarray analysis using Agilent Mouse microarray. To confirm microarray data, 6 genes (IL-1F6, iNOS, IL-10, Fabp4, IL-1RN and CSF2) were selected and performed RT-PCR and quantitative real-time PCR analysis with gene specific primers. The results of RT-PCR and real-time PCR agreed with microarray data. Overall, our results suggest that rice wine lees can be a novel resource for the development of foods and drugs which possess anti-inflammatory activity.