CONTEXT: Punica granatum L (Punicaceae) flower is an important diabetes treatment in oriental herbal medicine. OBJECTIVE: This study investigates the inflammation effects of pomegranate flower (PFE) ethanol extract in LPS-induced RAW264.7 cells. MATERIALS AND METHODS: PFE (10, 25, 50, 100mug/mL) was applied to 1mug/mL LPS-induced RAW 264.7 macrophages in vitro. Levels of nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines interleukin (IL)-1beta (IL-1beta), interleukin (IL)-6 (IL-6) and tumor necrosis factor (TNF-alpha) in the supernatant fraction were determined using enzyme-linked immunosorbent assay (ELISA). Expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), phosphorylation of mitogen-activated protein kinase (MAPK) subgroups extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and P38, as well as nuclear factor-kappaB (NF-kappaB) activation in extracts were detected via Western blot. RESULTS: 10-100mug/mL PFE decreased the production of NO (IC50 value=31.8mug/mL), PGE2 (IC50 value=54.5mug/mL), IL-6 (IC50 value=48.7mug/mL), IL-1beta (IC50 value=71.3mug/mL) and TNF-alpha (IC50 value=62.5mug/mL) in LPS-stimulated RAW 264.7 cells significantly. A mechanism-based study showed that phosphorylation of ERK1/2, p38, JNK and translocation of the NF-B p65 subunit into nuclei were inhibited by the PFE treatment. DISCUSSION AND CONCLUSION: These results show that PFE produced potential anti-inflammatory effect through modulating the synthesis of several mediators and cytokines involved in the inflammatory process.