Response surface methodology (RSM) was used to optimize the extraction process of 5-hydroxytryptamine (5-HT) from Hippophae rhamnoides Linn. seed meal with acetic acid.The optimal extraction conditions were as follows:acetic acid concentration 2.6%,liquid-solid ratio 50 mL/g,extraction temperature 100 ℃,extraction time 60 min and 1 time.Under the conditions,the extraction yield of 5-HT was 2.42 ± 0.04 mg/g.The 5-HT was enriched by macroporous adsorption resin.Meanwhile,lipopolysaccharide (LPS)-induced inflammatory model on RAW 264.7 mouse monocytes-macrophages was established to investigate the anti-inflammatory activity of the 5-HT fraction.The mechanism was also discussed.The results showed that 5-HT fraction inhibited the secretion of NO and inflammatory cytokines IL-6 and TNF-α,decreased the expression of COX-2 protein and inhibited the phosphorylation of IκBα protein,which significantly inhibited the inflammatory response induced by LPS.