Early weaning induces villous atrophy in the small intestine of piglets. We evaluated an influence of early weaning at 16 days old in mice for the use of villous atrophy model observed in early-weaned piglets. Five pregnant BALB/c mice were obtained and half of pups were weaned at 16 days old (early-weaned), while the others were allowed to suckle. Their small intestine was collected at 17, 18 and 19 days old in each group. Villous was shorting at 17 and 18 days old, but obscured at 19 days old. The gene expressions of epidermal and platelet-derived growth factor were associated with the villous height. Early weaning induced villous atrophy in the mouse small intestine as well as the piglets.