Tumor angiogenesis play a significant role in genesis, development and metastasis of pancreatic cancer though the process is different from angiogenesis in normal tissues. VEGF, one of the most important angiogenesis factors, is modulated by inflammation factors as well as transcriptional factors, such as members of Sp/KLF family. Recent research showed that VEGF related inflammation factors and Sp/KLF family members form a complex network structure, which causes genesis and development of tumor. Conceivably, fully understanding the mechanism linking VEGF related inflammation factors and Sp/KLF family members would promote the concept of tumor angiogenesis. Furthermore, it could also help to design effective strategies to target the key components of the network and control the development and progression of tumor.