〔Abstract〕 Objective To investigate the protective effect and mechanism of Hudi Enteric capsules in ionizing radiation injury to small intestinal crypt cells(IEC-6 cells) in rats. Methods IEC-6 cells were irradiated with 6 mega electron volt X-rays(2, 4, 6, 8 and 10 Gy), cell clone formation assay was used to detect cell proliferation, and the 6 Gy ionizing radiation was selected to establish a cellular radiation damage model according to the cell survival rate. The effect of each concentration(12.5, 25, 50, 100 and 200 μg/ml) of Hudi enteric extract on the viability of IEC-6 cells was examined by cell counting kit-8(CCK-8) method, and the effect on the viability of IEC-6 cells after irradiation at(10, 20, 40 and 80 μg/ml) concentrations was examined according to the results.After obtaining the optimal irradiation dose and extract concentration, the cells were divided into control group, model group and Hudi extract group(80 μg/ml), the control group was pseudo-irradiated and the other two groups received 6 Gy of ionizing radiation, and the Hudi enteric extract group was pre-treated with drugs 2 h before irradiation. Apoptosis was detected by Annexin V-PI double staining; cell senescence was detected by β-galactosidase(β-Gal) staining; reactive oxygen species was detected by DCFH-DA fluorescent probe; the corresponding protein expression of p16, p21, Catalase(CAT) and Superoxide dismutase(SOD2) was detected by Western blot.Results The proliferation of IEC-6 cells was inhibited by radiation doses ranging from 4 Gy to 10 Gy(P<0.001);the concentrations of 40 and 80 μg/ml of Hudi enteric extract increased the survival rate of irradiated IEC-6 cells(P<0.001), and the apoptosis rate, β-Gal positivity rate and DCFH-DA fluorescence intensity in the Hudi enteric extract group were lower than those in the model group(P<0.05). The protein expressions of CAT and SOD2 in the Hudi extract group were higher than those in the model group(P<0.05), and the protein expressions of p16 and p21 were lower than those in the model group(P<0.05).Conclusion The mechanism of action of Hudi enteric capsules that attenuate radiation damage in IEC-6 cells may be related to the inhibition of reactive oxygen species production, reduction of oxidative stress, and attenuation of cellular senescence and apoptosis.