Endoplasmic reticulum (ER) stress-associated inflammation positively induces many diseases, including insulin resistance. Fucosylated chondroitin sulphate from Acaudina molpadioides (Am-CHS) can mitigate insulin resistance. However, its effects on ER stress and inflammation are unclear. We investigated whether Am-CHS influenced ER stress, inflammatory cytokines, and JNK and IKK beta/NF kappa B pathways in insulin resistant mice. Am-CHS lowered serum and hepatic ROS, NO, and FFA levels. Meanwhile, Am-CHS decreased serum proinflammatory cytokines TNF-alpha, CRP, MIP-1, IL-1 beta and IL-6 concentrations and their hepatic mRNA expression, and increased anti-inflammatory cytokine IL-10 levels. Am-CHS reduced ER stress markers Bip, ATF6, PERK, and XBP1 mRNA or protein expression, and PERK, eIF2 alpha, and IRE1 alpha phosphorylation. These reductions were accompanied by reduced JNK1 and IKK beta activation, NF kappa B nuclear translocation, and IR/IRS-2 serine phosphorylation in Am-CHS-treated mice. These findings suggest that Am-CHS could be an alternative against inflammation and ER stress as a functional food ingredient and natural health product. (C) 2015 Elsevier Ltd. All rights reserved.