Abstract: N-acetylglucosamine transferase-4a (GnT-IVa) is an indispensable glycosyltransferase for the formation of N-glycan branch complex of glucose transporter 2 (GLUT2) in pancreatic beta cells, which sits the N-glycan branch complex on the surface of cell membranes to perform its normal physiological functions. The previous work of this research group indicates that geniposide can rapidly regulate the glycosylation of GLUT2 and glucose uptake in pancreatic beta cells, but whether GnT-IVa is directly related to it is still not clear. This paper firstly uses siRNA to interfere GnT-IVa expression of INS-1 cells, and then analyzes the effect of geniposide on the glycosylation of GLUT2, glucose uptake and metabolism, and glucose-stimulated insulin secretion (GSIS). The results reveal that, in INS-1 cells interfered by GnT-IVa genes, the effects of geniposide on the glycosylation of GLUT2, glucose uptake, ATP production and GSIS are significantly attenuated. All these findings indicate that GnT-IVa may play an important role in geniposide regulating the glycosylation of GLUT2, glucose uptake and metabolism, and GSIS in pancreatic beta cells.