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Background: Liangxue Guyuan decoction (LGD) has been used to alleviate symptoms of radiation enteritis (RE) in the clinic. This study aimed to investigate the effects and anti-apoptosis and proliferative mechanisms of LGD in rats with RE. Materials and Methods: A total of 115 male Sprague Dawley rats were used. The control group consisted of 15 rats, and the remaining 100 rats were irradiated with 60 Co γ rays at a dose of 11 Gy and randomly divided into four groups of 25 each: the model group, the dexamethasone (DXM) group, the low-dose LGD (LGDl) group, and the highdose LGD (LGDh) group. The treatment was administered intragastrically for 7 days, and the number of rats that died was recorded daily. On days 3 and 7 after irradiation, five rats were randomly chosen and sacrificed from each group, and ileum samples were taken for pathological observation, immunofluorescence staining, western blotting, and PCR experiments. Results: Compared with the model group, the mean survival time, villus length (V), and the ratio of V to crypt depth C (V/C), the number of Ki67positive cells was increased, and the number of TUNEL-positive cells was reduced in the LGDh group. In addition, LGDh showed some effects on upregulating p-PI3K, p-AKT, and Bcl-2 and downregulating caspase-3 and Bax. The effect of LGD was better than that of DXM. Conclusions: LGDh prolonged the survival time of irradiated rats, inhibited intestinal epithelial cell apoptosis, and promoted intestinal repair. This mechanism may be related to the regulation of the PI3K/AKT pathway.