To investigate the intervention effect of Dendrobium nobile polysaccharides on NAFLD rats，and to analyze the mechanism of action from the NLRP3 signaling pathway.Methods:A total of 72 SD rats were divided into 6 groups，which were the normal，model，high dose，medium dose，low dose Dendrobium nobile polysaccharide，and the polyene phosphatidylcholine intervention group.Except for the normal group，the other 5 groups were constructed an animal model of NAFLD and after treatment，the rats were sacrificed.Their liver was taken out to detect liver pathology and NLRP3，Caspase-1 protein and mRNA expression.Their blood was also collected to detect the AST，ALT，TG，TC，LDL-C，HDL-C，IL-1β and IL-18.Results:The liver lobules in the normal group were clear，and the nuclei were evenly distributed.The model group had obvious fatty vacuoles and inflammatory reaction infiltration.The Dendrobium nobile polysaccharide and polyene phosphatidylcholine group improved significantly.Compared with the control group，AST，ALT，TG，TC，HDL-C，LDL-C，IL-1β，IL-18，Caspase-1 and NLRP3 protein and mRNA were significantly increased in the model group(P<0.05).Compared with the model group，those indexes in the Dendrobium nobile polysaccharide and the polyene phosphatidylcholine group were significantly lower(P<0.05).In addition，there was no difference in AST，ALT and HDL-C between the Dendrobium nobile polysaccharide group and the polyene phosphatidylcholine group.TG，TC and LDL-C of the high-dose group were lower than those of the polyene phosphatidylcholine group(P<0.05).The protein and mRNA of IL-1β，IL-18，Caspase-1 and NLRP3 in the high-dose group were significantly lower than those in the polyene phosphatidylcholine group(P<0.05).Conclusion:Dendrobium nobile polysaccharides can significantly improve the liver function and blood lipids of NAFLD rats induced by a high-fat and high-sugar diet，which is related to its ability to regulate the inflammasome NLRP3，thereby reducing the inflammatory response.