Objective: To establish a model of weaning human floral-associated mice and study on the effect of intestinal flora on the grouth and development of mice. Methods: The intestinal flora of weaned infants was transplanted into germ free Kunming mice to establish a model of weaning human floral-associated mice. Weaning mice with human flora and germ free mice (n=9， for each group) were fed with basic diet until 8 weeks old. The body weight， brain fatty acid content， insulin-like growth factor-1 (IGF-1) and in-sulin-like growth factor binding protein-3 (IGFBP3) contents in serum and liver were measured. The development of hippocampal CA1 area and colon were observed by HE staining. The differences of indexes between the two groups were compared， and the effects of intestinal flora on brain， intestinal development and immunity were analyzed. Results: The weaning human floral-associated mice were in good health and could partially simulate the intestinal flora of weaning infants. Intestinal flora had significant effects on the development of mice brain neuronal cells， synapses and colonic villi. The contents of monounsaturated fatty acids C16∶1(P < 0.001)， C18∶1 (P < 0.01) and polyunsaturated fatty acids C18∶3 (P < 0.05)， C20∶3 (P < 0.01)， C20∶4 (P < 0.001)， C22∶5 (P < 0.05) and C22∶6 (P < 0.01) in mouse brain were significantly affected. It had a significant effect on the content of IGF-1 in serum and liver of mice. Conclusion: The weaning human floral-associated mice provides an effective animal model for the study of the effect of intestinal flora on host physiological function in weaning infants.