Pancreatic cancer (PC) is a malignancy of gastrointestinal tract threatening the life of people around the world. In spite of the advances in the treatment of PC, the overall survival of this disease in advanced stage is less than 12%. Moreover, PC cells have aggressive behaviour in proliferation and metastasis as well as capable of developing therapy resistance. Therefore, highlighting the underlying molecular mechanisms in PC pathogenesis can provide new insights for its treatment. In the present review, inflammation and related pathways as well as role of gut microbiome in the regulation of PC pathogenesis are highlighted. The various kinds of interleukins and chemokines are able to regulate angiogenesis, metastasis, proliferation, inflammation and therapy resistance in PC cells. Furthermore, a number of molecular pathways including NF-κB, TLRs and TGF-β demonstrate dysregulation in PC aggravating inflammation and tumorigenesis. Therapeutic regulation of these pathways can reverse inflammation and progression of PC. Both chronic and acute pancreatitis have been shown to be risk factors in the development of PC, further highlighting the role of inflammation. Finally, the composition of gut microbiota can be a risk factor for PC development through affecting pathways such as NF-κB to mediate inflammation.