Berchemia floribunda (Wall.) Brongn. (BF), which belongs to Rhamnaceae, is a special plant of Anmyeon Island in Korea. BF has been reported to have antioxidant and whitening effects. However, the anti-inflammatory activity of BR has not been elucidated. In this study, we evaluated the anti-inflammatory effect of leaves (BR-L), branches (BR-B) and fruit (BR-F) extracted with 70% ethanol of BR and elucidated the potential signaling pathway in LPS-induced RAW264.7 cells. BR-L showed a strong anti-inflammatory activity through the inhibition of NO production. BR-L significantly suppressed the production of the pro-inflammatory mediators such as iNOS, COX-2, IL-1β, IL-6 and TNF-α in LPS-stimulated RAW264.7 cells. BR-L suppressed the degradation and phosphorylation of IκB-α, which contributed to the inhibition of p65 nuclear accumulation and NF-κB activation. BR-L obstructed the phosphorylation of MAPKs (ERK1/2, p38 and JNK) in LPS-stimulated RAW264.7 cells. Consequently, these results suggest that BR-L may have great potential for the development of anti-inflammatory drugs to treat acute and chronic inflammatory disorders.