In this study, we showed the crucial role of intestinal epithelial cell Gastrin/CCKBR axis in the pathogenesis of T2D by selectively silencing and stimulating intestinal CCKBR with gavage of Gastrin‐SiO2 microspheres in Villin‐Cckbr−/− mice. The gene discussed is GAST; the disease is type 2 diabetes mellitus.