Coprophagy is of great significance to the growth, development, and reproductive performance of rabbits. This study is aimed at exploring the effect of coprophagy on the reproductive performance of New Zealand white rabbits by coprophagy prevention (CP). The results showed that CP treatment significantly decreased the growth and development performance of female rabbits and the live birth rate of embryos. The results of blood biochemical indexes showed that CP treatment significantly increased the contents of serum ALB, ALP, and MDA, while serum SOD activity was significantly decreased. Transcriptome analysis showed that GO terms were mainly enriched in transport function and reproductive function after CP treatment. In addition, KEGG results showed that inflammation related signal pathways were activated and the expression level of genes related to tight junction proteins was downregulated by CP treatment. Concurrently, western blot further confirmed the results of KEGG. In short, fecal feeding is an important survival strategy for some small rodents, coprophagy prevention will affect the inflammatory level of the body, change the oxidative stress level of the body, and then activate NOX4-ROS-NF-κB pathway, increase the expression level of adhesion protein ICAM-1 and VCAM-1, lead to the damage of uterine epithelial barrier, and then affect the reproductive performance of rabbits.