Objective: To investigate the effects of melatonin on cellular proliferation and endogenous vascular endothelial growth factor (VEGF) expression in pancreatic carcinoma cells (PANC-1). Methods: PANC-1 cells were cultured for this study. The secreted VEGF concentration in the culture medium was determined using ELISA method, VEGF production in the tumor cells was detected by immunocytochemistry, and VEGF mRNA expression was determined by RT-PCR. Results: Higher melatonin concentrations significantly inhibited cellular proliferation, with 1 mmol/L concentration exhibiting the highest inhibitory effect (P<0.01). VEGF concentrations in the cell culture supernatants and intra-cellules were all significantly reduced after melatonin (1 mmol/L) incubation (P<0.05). VEGF mRNA expression decreased markedly in a time-dependent manner during the observation period (P<0.05). Conclusions: High melatonin concentrations markedly inhibited the proliferation of pancreatic carcinoma cells. The endogenous VEGF expression was also suppressed by melatonin incubation.