The inhibitory effects of epicatechin on lipopolysaccharide (LPS)-induced production of pro-inflammatory mediators in RAW264.7 cells were estimated in the study. The results show that epicatechin could down-regulate the expressions of inducible nitric oxide synthase and cyclooxygenase-2 as well as the productions of nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines (interleukin-1β [IL-1β], IL-6 and tumor necrosis factor-α [TNF-α]) in LPS-induced RAW264.7 cells. The attenuation of LPS-induced inflammatory responses in RAW264.7 cells by epicatechin was found to be closely correlated with inhibition of activation of an inhibitor of κB kinase α/β and sequential translocation of nuclear factor-κB (NF-κB) p50/P65 subunits. Moreover, the suppression of activation of mitogen-activated protein kinases (MAPKs) (including extracellular signal-regulated kinase [ERK], Jun N-terminus kinase [JNK] and p38) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) was also involved in the anti-inflammatory effects of epicatechin. Practical Applications: Epicatechin is a major polyphenolic component with effective antioxidant activity in litchi flowers. Antioxidant and radical scavenging activities of phytochemicals might contribute to their anti-inflammatory actions. The results of our study suggest that epicatechin effectively attenuates the production of inflammatory mediators including NO, PGE2, TNF-α, IL-1β and IL-6 in the LPS-induced macrophages through inactivation of NF-κB, MAPKs (ERK, JNK and p38) and JAK2/STAT3 pathways. Litchi flowers might have the potential for anti-inflammation through suitable treatment.