Objective:To explore the protective effects and related mechanism of tea saponin (TS) on intestinal inflammation due to Shigella infection. Methods:In vitro, the antibacterial activity of TS was detected by standard broth microdilution method. The absorbance at 600 nm of the bacterial liquid was detected by Microplate Reader under different concentrations of TS, and the growth curve was drawn. Bacterial count was obtained by plate colony counting. In vivo, 15 mice were divided into 3 groups ( n=5 each): control group, Sf301 group and TS group. Sterile water or TS was applied to mice in the Sf301 group and the TS group per gavage once a day for 8 days, and the mouse model of Shigella infection was established on day 3. The disease activity index (DAI) was used to evaluate the general condition of mice. The mice were sacrificed on day 8. Colon length was measured and colon tissues were stained with HE to analyze the pathological changes. The cecal contents and feces of mice were taken for plate counting and Shigella load was obtained. Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the mRNA expression levels of inflammatory factors. Results:(1) In vitro, the MIC of TS was 1 024 μg/ml. The plate counting and A600 of TS decreased in proportion to increasing concentrations (256, 512, 1 024 μg/ml) in comparison with the control group (all P<0.05). (2) In vivo, colon length was (7.70±0.24) cm in the control group and (7.35±0.41) cm in the TS group, which was significantly longer than that of the Sf301 group ([6.13±0.05] cm, P<0.05). Histopathological examination evidenced colonic epithelial cells shedding, decreased goblet cells, and inflammatory cell infiltration in the colon tissue of the Sf301 group. In the TS group, the colonic mucosa was intact without significant inflammatory cell infiltration. Bacterial load in cecal contents was significantly lower in the TS group than in the Sf301 group ( P<0.05). The level of tumor necrosis factor-α was significantly lower, and the level of interleukin-10 was significantly higher in the TS group than in the Sf301 group (all P<0.05). Conclusion:TS can effectively inhibit Shigella and alleviate Shigella infective enteritis by reducing Shigella load and inhibiting inflammation.