Abstract: Objective :To investigate hypermethylation of claudin5 (CLDN5) and neuronal pen-traxin Ⅱ(NPTX2) in pure pancreatic juice(PPJ) endoscopically aspirated from patients with pancreaticcancer(PCa) and chronic pancreatitis (CP),and to evaluate their clinical significance in diagnosing hu-man pancreatic cancer. Methods :Methylation-specific polymerase chain reaction (MSP) was used to de-tect hypermethylation of CLDN5 and NPTX2 in PPJ from 21 patients with PCa and 8 patients with CP. Results : Hypermethylation of CLDN5 was found in 81.0%(17/21) and hypermethylation of NPTX2 wasfound in 71.4%(15/21) of PPJ samples from patients with PCa. In patients with CP, 12.5%(1/8) showedhypermethylation of either of the 2 genes. Hypermethylation of NPTX2 and CLDN5 was significantlydifferent between PCa and CP (P<0.05). Conclusion :Hypermethylation of NPTX2 and CLDN5 mightbe a molecular marker to distinguish between malignant and benign disease of the pancreas.