Cerulein pancreatitis is similar to human edematous pancreatitis with dysregulation of the digestive enzyme production and cytoplasmic vacuolization, the death of acinar cells, edema formation, and an infiltration of inflammatory cells into the pancreas. Our preliminary proteomic analysis showed increased expression of vascular endothelial growth factor-D (VEGF-D) in cerulein (10 -8M)-treated pancreatic acinar cells. We hypothesized that VEGF-D may have a role in cerulein-induced cytokine expression in pancreatic acinar cells. This article was designed to elucidate whether cerulein induces VEGF-D expression in pancreatic AR42J cells, and whether VEGF-D expression is related to interleukin-6 (IL-6) expression by transfecting antisense oligonucleotide (AS ODN) for VEGF-D into pancreatic acinar AR42J cells. Cerulein-induced AP-1 activation was monitored in the cells transfected with AS ODN or sense ODN (S ODN) for VEGF-D. mRNA expression of IL-6 was determined by RT-PCR analysis. AP-1 activation was assessed by electrophoretic mobility shift assay (EMSA). VEGF-D expressionwas assessed by Western blotting. Cerulein induced IL-6 expression and VEGFD expression in AR42J cells. Cerulein-induced AP-1 activation and IL-6 expressionwas inhibited in the cells transfected with ASODN for VEGFD as compared to S ODN. Cerulein-induced VEGF-D expression may have a role in AP-1 activation and IL-6 expression in pancreatic acinar cells.