Increasing pressure of life may bring some disease risks and stress injuries, which may destroy the immune system and result in intestinal mucosal immune disorders. In this study, the effects of different doses of ATX (30 mg per kg b.w., 60 mg per kg b.w. and 120 mg per kg b.w.) on intestinal mucosal functions were explored in cyclophosphamide (Cy)-induced immunodeficient mice. The results showed that continuous intraperitoneal injection of 100 mg per kg b.w. Cy for three days led to a persistent decrease of body weight and a range of abnormalities in the intestine of C57BL/6 mice. However, administration of ATX at 60 and 120 mg per kg b.w. could effectively prevent intestinal mucosa from this damage, including reduced levels of oxidative stress (MDA, GSH and GSH-PX), increased intestinal morphological structural integrity, stimulative growth of goblet cells and mucous secretion, decreased development of Paneth cells and expression levels of antimicrobial peptides (AMPs) (Reg-3γ and lysozyme), increased IgA secretion, ameliorative main gut flora (especially total bacteria, Lactobacillus and Enterobacteriaceae spp. ) and its metabolites (acetic acid, propionic acid and butyric acid). These protective effects of ATX were better than those of control-β-carotene in general. Our results may provide a new protective measure to keep intestinal mucosal barriers, which is of great significance for maintaining immune function in the body.