Objective To investigate the effect of Changfukang prescription on general condition and apoptotic genes in the small intestinal mucosa in rats with acute radiation enteritis. Methods An X-ray linear accelerator was used to perform total abdominal irradiation for experimental rats to establish the rat model of acute radiation enteritis. The experimental rats were randomly divided into normal control group, model control group, and low-, medium-, and high-dose Changfukang groups. After the model was successfully established, all rats in the low-, medium-, and high-dose Changfukang groups were given 10 mL/kg Changfukang decoction by gavage, equivalent to doses of the crude drug of 15.75 g/kg, 31.50 g/kg, and 63.00 g/kg, respectively, as was determined by dose conversion. The rats in the model control group and the normal control group were given normal saline of the same volume by gavage. All the rats were treated by gavage for 30 days continuously. The mental state, food and water intake, defecation, and change in body weight were observed. After the rats were sacrificed, the corresponding small intestinal tissues were harvested, and immunohistochemistry and Western blot were used to measure the expression of apoptotic genes Caspase-3, Bax, and Bcl-2 in small intestinal epithelial cells. Results Compared with the model control group, the Changfukang groups showed significant improvements in the mental state, food and water intake, and defecation, as well as significant increases in body weight, and the medium-dose Changfukang group showed the best response (P<0.05). Compared with the model control group, the low-, medium-, and high-dose Changfukang groups showed significantly downregulated expression of Caspase-3 and Bax, a significant decrease in Bax/Bcl-2 ratio, and significantly upregulated expression of Bcl-2 (P<0.05), and the medium-dose Changfukang group showed the best response.Conclusion Changfukang prescription can improve the general condition of rats with acute radiation enteritis and inhibit cell apoptosis, and the medium-dose Changfukang decoction has the best effect. Its mechanism may be related to downregulation of the expression of apoptotic genes Caspase-3 and Bax, upregulation of the expression of Bcl-2, and inhibition of cell apoptosis in small intestinal epithelial cells.