Abstract: The protective effects of Ganoderma atrum polysaccharide(PSG) on acute intestinal inflammation caused by lipopolysaccharide(LPS) were investigated. Rats were randomly divided into a control group(Con), a model group(LPS), positive control group(DEX) and three groups treated with PSG: Low-dose group(PSG-20), middle-dose group(PSG-40) and high-dose group(PSG-80), with 10 rats in each group. Rats were orally administered either vehicle(0.9% saline) alone or vehicle composition containing PSG(20, 40, and 80 mg/kg/d) for 7 days. After intragastric administration on the 7th day, 0.8 mg/kg LPS was injected intraperitoneally to establish an acute intestinal inflammation model. The results indicated that PSG has an anti-inflammatory effect on LPS-induced rats by observing jejunum histology, detecting the content of IL-1β and IL-10 in intestinal tissue. Compared with LPS group, the morphology of the jejunum tissue and the content of IL-1β and IL-10 were adjusted to normal levels. Furthermore, the metabolic effects of PSG were evaluated by screening and identifying differential metabolites and exploring metabolic pathways in rats based on UPLC-Q-TOF/MS metabolomics analysis. Accordingly, results indicated that 22 metabolites were significantly(P<0.05) changed in acute intestinal inflammation rats when compared to control rats. Meanwhile, PSG pretreatment could restore 12 different metabolites such as PC(24: 0/20: 4(5Z, 8Z, 11Z, 14Z)), DG(16: 0/20: 3(5Z, 8Z, 11Z)/0:0), and then participated in three metabolic pathways of glycerophospholipid metabolism, linoleic acid metabolism and α-linolenic acid metabolism, exerting its anti-inflammatory effects on LPS-induced rats. Altogether, PSG could improve LPS-induced acute intestinal inflammation and its mechanism were linked to inhibit release of proinflammatory mediators and reverse metabolic pathway disturbances