We evaluate the effects of the Chaihu-Shugan-San decoction on intestinal microbe dysbiosis and chronic metabolic inflammation via the NLRP3 pathway in NAFLD rats that were fed a high-fat diet. Twenty-four SD rats (male, six weeks old, 200 ± 20 g) were randomly divided into three groups: normal control group (NC group), high-fat diet-fed group (HFD group), and Chaihu-Shugan-San decoction intervention group (CH group). The NC group rats were given standard feed, the HFD group rats were all fed a high-fat diet (83% standard feed + 10% lard oil + 5% sucrose + 1.5% cholesterol + 0.5% cholate), and the CH group rats were given a HFD plus Chaihu-Shugan-San at 9.6 g•kg-1•d-1. Body composition, serum and liver lipids, inflammatory markers, intestinal microbial population, and the NLRP3 pathway-associated protein were assessed. The results showed that Chaihu-Shugan-San decoction significantly reduced body weight and total fat mass and the levels of serum LPS, TG, TNF-α, IL-1β, and IL-18, as well as liver TC, TG, TNF-α, IL-1β, and IL-18 (P < 0.05). The abundance of Enterobacteriaceae (0.375% versus 0.064%, P < 0.05), Staphylococcaceae families (0.049% versus 0.016%, P < 0.05) and Veillonella genus (0.096% versus 0.009%, P < 0.01) significantly decreased, whereas the abundance of Anaeroplasma genus (0.0005% versus 0.0178%, P < 0.01) significantly increased. The expression levels of NLRP3, ASC, and Caspase-1 were changed significantly (P < 0.05). In summary, the Chaihu-Shugan-San decoction modulated intestinal microbe dysbiosis, reduced fat accumulation, and alleviated inflammatory factor expression, which are all processes related to the NLRP3 inflammasome pathway in NAFLD rats.