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Objective:To examine whether Caulerpa okamurae ethanolic extract (COE) could inhibit obesitymediated inflammation,improve glucose metabolism and increase insulin sensitivity,using in vitro cell models of RAW 264.7 macrophages and 3T3-L1 adipocytes.Methods:We cocultured 3T3oL1 adipocytes in direct contact with lipopolysaccharide-stimulated RAW 264.7 macrophages and induced insulin resistance in 3T3-L1 adipocytes with tumor necrosis factor-α (TNF-α) in the presence or absence of 250 μg/mL of COE.We investigated various markers of inflammation,glucose regulation and insulin sensitivity in these models using Griess reagent to measure nitric oxide (NO) production,2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose to measure glucose uptake,West blot analysis to quantify protein expression and reverse transcriptasepolymerase chain reaction to evaluate mRNA expression.Results:We found that COE (250 μg/mL) significantly inhibited the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages by downregulating NO production,nitric oxide synthase 2 expression and nuclear translocation of nuclear factor-κB.COE also showed similar anti-inflammatory activity in coculture,along with decreased TNF-α,interleukin-6 and monocyte chemoattractant protein mRNA expression.In addition,COE also improved glucose uptake in coculture by upregulating glucose transporter-4 (GLUT-4) and adiponectin and reducing serine phosphorylation of insulin receptor substrate-1 (IRS1).In the TNF-α-induced insulin resistance model of 3T3-L1 adipocytes,COE significantly improved both basal and insulin-stimulated glucose uptake,accompanied by phosphorylation of IRS1 at tyrosine 632,phospho-5′ adenosine monophosphate-activated protein kinase α and glycogen synthase kinase-3β (Serg) as well as upregulation of GLUT-4.Conclusion:Together,these findings suggest that COE has potential to treat or prevent obesity-induced metabolic disorders.