Diabetes mellitus is a serious threat to human health.Cyclocarya paliurus(Batal.)Iljinskaja(C.paliurus)is one of the traditional herbal medicine and food in China for treating type 2 diabetes,and the C.paliurus polysaccharides(CP)were found to be one of its major functional constituents.This research aimed at investigating the hypoglycemic mechanism for CP.It was found that CP markedly attenuated the symptoms of diabetes,and inhibited the protein expression of Bax,improved the expression of Bcl-2 in pancreas of diabetic rats,normalized hormones secretion and controlled the inflammation which contributed to the regeneration of pancreatic β-cell and insulin resistance.CP treatment increased the beneficial bacteria genus Ruminococcaceae UCG-005 which was reported to be a key genus for protecting against diabetes,and the fecal short-chain fatty acids levels were elevated.Uric metabolites analysis showed that CP treatment helped to protect with the diabetes by seven significantly improved pathways closely with the nutrition metabolism(amino acids and purine)and energy metabolism(TCA cycle),which could help to build up the intestinal epithelial cell defense for the inflammation associated with the diabetes.Our study highlights the specific mechanism of prebiotics to attenuate diabetes through multi-path of gut microbiota and host metabolism.