Hyperglycemia promotes pancreatic cancer progression, while the underlying mechanism is uncertain. We investigated the cell proliferation, glial cell line-derived neurotrophic factor (GDNF) and its tyrosine kinase receptor RET expression in BxPC-3 and MIA PaCa-2 cells when exposed to different concentrations of glucose. Proliferation of both cells was effected by glucose in a concentration-dependent manner. Definite expression of GDNF and RET was detected in both cells. Glucose concentrations could alter the expression of GDNF and RET in a concentration-dependent manner, correspondingly with the alterations of cell proliferation. Up-regulation of GDNF and RET ligand-receptor interaction might participate in the glucose-induced cancer progression.