In the present study we investigated the anti-inflammatory activity of Japanese quince leaf polyphenol-rich extract (JQLPE) in lipopolysaccharide (LPS)-activated murine macrophages (RAW 264.7). The Q-PCR analysis revealed that JQLPE decreased Nfkb1, Ptgs2, and Il1b expression at the mRNA level by 80%, 50% and 48%, respectively. Similarly, JQLPE significantly attenuated expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) (by 60%, 50%, 67%, 37% and 36%, respectively) at the protein level and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7. Western blot also showed that the expression of nuclear factor kappaB (NF-κB) p65 and p-NF-κB p65 was down-regulated after JQLPE treatment. These results provide the first evidence that JQLPE decreases the expression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), inflammatory mediators (COX-2, iNOS) and both NF-κB p65 and p-NF-κB p65 in LPS-stimulated RAW264.7 cells, which may suggest its anti-inflammatory activity.