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Background Enriched environment is a paradigm where animals are introduced to novel, complex, and stimulating surroundings that can protect the intestinal mucosal barrier and regulate the expression of brain-gut peptides. Probiotics can effectively protect the intestinal mucosal barrier and regulate brain-gut axis activity in colorectal cancer patients. This study assessed the effects of probiotics, enriched environment, and joint intervention on the intestinal mucosal barrier and brain-gut axis in rats with colorectal cancer. Methods We used a rat model of 1,2-dimethylhydrazine-induced colorectal cancer. Rats were housed in four different conditions for 2 weeks: enriched environment, probiotic,joint condition and normal condition. Each rat was weighed, and the intestinal mucosa and plasma levels of tumor TNF-α, IL-6, IL-10, ghrelin, CRF, occludin, BT, SIgA and the morphology of the intestinal mucosa were measured. Results enriched environment was beneficial regarding bacteria translation, plasma and intestinal mucosa levels of cytokines, plasma CRF levels, villi length and width of intestinal mucosa and hypothalamus ghrelin compared to probiotic (P 0.05). Conclusions The effect of enriched environment was better than probiotic, especially in the intestinal mucosal immune and biological barrier in rats with colorectal cancer. However, the combination of the two was not as effective as enriched environment. In future studies, we can investigate the role of environment and probiotics in SIgA, intestinal mucosal mechanical barrier and body weight by extending the intervention time and enlarging the sample size.