BACKGROUND This study reports the influence of CXCL12 and its receptor CXCR4 on the progression of pancreatic cancer and illuminates the correlation between the CXCL12/CXCR4 axis and the angiogenesis and lymphangiogenesis of pancreatic adenocarcinoma (PAC). METHODS A total of 30 patients with pancreatic cancer participated in the current study. The expression of CXCL12 and CXCR4 in cancerous tissues, paracancerous tissues, normal pancreas, and lymph nodes surrounding the pancreas were investigated using real-time PCR and immunohistochemistry, respectively. In addition, we assessed microvessel density (MVD) and microlymphatic vessel density (MLVD) in tumor tissues using immunohistochemistry. RESULTS CXCL12 expression in tumor tissues was significantly lower than that of paracancerous tissues, normal pancreas, and lymph nodes. In contrast, CXCR4 expression in cancerous tissues was considerably higher than that of normal pancreas. Additionally, a significant correlation between the expression pattern of the CXCL12/CXCR4 axis and clinicopathologic features, such as lymph node metastasis, was identified. Furthermore, we found that CXCL12 expression was significantly associated with MVD but not significantly associated with MLVD, while CXCR4 expression was significantly associated with MLVD but not significantly associated with MVD. CONCLUSIONS The chemotactic interaction between CXCR4 and its ligand CXCL12 may be a critical event during the progression of pancreatic cancer. The underlying mechanism may be the induction of angiogenesis and lymphangiogenesis regulated by the interaction of CXCL12 and CXCR4.