Background: Early-weaned in Rex rabbits and other animals is associated with the development and immunity of intestine. This article was aimed to investigate the potential benefits of a dietary supplementation, modified Si-jun-zi granule (M-SJZG), on enhancing immunity of small intestinal mucosa and promoting intestinal development of weaned Rex rabbits. Results: In the present study, we found that dietary supplementation with 2% modified Si-jun-zi granule decreased the diarrhea frequency and mortality due to early-weaned, and significantly increased the average daily gain; the length and relative weight of intestine; the concentration of immunoglobulin in serum and SIgA in intestinal mucus. Additionally, the activity of lipase was raised by dietary Si-jun-zi granule addition. However the activities of ALT, ALP and AST in serum were obviously decreased. Compared with the un-supplementation control group, the ratio of villi length to crypt depth and the expression of tight junction protein(zonula occludens-1, Claudin-1 and Occludin) and Glucose transporter (re-combinant Sodium/Glucose co-transporter 1 and recombinant Glucose transporter 2) in jejunum were raised. In addition, Moreover early development of intestine and the injury of intestinal mucosa induced by early-weaning also could be improved.Conclusions: This study indicated that modified Si-jun-zi granule has protective effects on diarrhea induced by early-weaning through enhancing immunity of small intestine mucosa and promoting intestinal development.