It has been suggested that pancreatic cancer is associated with a greater prevalence of depression than many other cancers, but the mechanism accounting for this potential association has not yet been illustrated. In the present study, conditioned media (CM) from three pancreatic cancer cell lines and primary pancreatic cancer cells from two patients were added to culture system of differentiated pheochromocytoma cell line PC12. The release of dopamine (DA) and norepinephrine (NE) by PC12 was significantly inhibited after CM treatment (P < 0.05), similar to what happened after recombinant interleukin 6(IL-6) treatment. Furthermore, pretreatment with anti-IL-6 antibody significantly blocked the inhibitory effects of pancreatic cancer CM on DA and NE production (P < 0.05). We also demonstrated that tyrosine hydroxylase (TH), the rate-limiting enzyme for synthesis of catecholamine, was reduced after exposure to IL-6, which was accompanied by JAK-STAT3 pathway activation. Our results demonstrated that IL-6 in CM from pancreatic cancer down-regulated the production of DA and NE by PC12 cell. The possible underlying mechanisms might be decreasing TH production via activation of JAK-STAT3 signal transduction pathway. The present study might help to better understand the close relationship between pancreatic cancer and depression.