Objective To investigate the therapeutic effects of Erqi decoction (EQD) for treatment of acute radiation enteritis in SD rats and the related mechanism. Methods A total of 53 SD rats were randomly divided into normal group model group, EQD group and Baitouwengtang(BTWT) group, with 8 rats in the normal control group and 15 in each of the rest groups. Rats in the latter three groups were exposed to a single dose of 10 Gy 6 MV higher-energy X-rays on the abdominal region to establish the acute radiation enteritis models. Then all the rats were intragastrically administered with corresponding agents for a consecutive of 7 days. Then 10 ml ileum samples in ileocecal junction were obtained from each animal under general anesthesia. The morphologic indices were examined by light microscopy and the image analysis system. The nitric oxide (NO) levels, superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in the small intestinal homogenates were measured by spectrophotometer. Results The EQD group had significantly higher villus height ([243±9] vs [211±21] μm ), deeper crypt ([171±12] vs [142±10] μm ), thicker mucosa ([460±21] vs [420±37] μm) and entire wall thickness ([609±19] vs [569±21] μm) than the model group (P＜0.05), and the above parameters were not significantly different between the EQD group and the BTWT group. EQ group had significantly lower NO level ([0.88±0.11] vs [1.65±0.12] μmol/g), higher MDA level ([3.20±0.12] vs [4.75±0.24] nmol/mg) and lower SOD activity ([212±13] vs [150±11] U/mg, P＜0.05) in the intestine compared with the model group (P＜0.05). EQD group had significantly lower NO and MDA levels and higher SOD activity compared with the BTWT group (P<0.05). Conclusion It is indicated that EQD has protective effect against intestine mucosa damage in acute radiation enteritis rat model by reducing the intestinal NO generation, improving intestinal SOD activity, reducing MDA generation. Anti-free radical injury may be one of the mechanisms for treatment of acute radiation enteritis.