Pancreatic cancer is a highly lethal and aggressive tumor that affects the digestive tract,leading to poor prognosis and low survival rate. At present,gemcitabine-based chemotherapy is widely used in the clinical treatment of pancreatic cancer. However,the efficacy of chemotherapy has significantly decreased with the emergence of clinical drug resistance. In order to meet its demand of energy and biological materials,tumors always change its metabolic pathway,which is called tumor metabolic reprogramming. The abnormal enhancement of aerobic glycolysis is one of characteristics of glucose metabolic reprogramming in pancreatic cancer cells. The glucose transporter proteins and key enzymes are participated in the processes and regulated chemotherapy resistance through different signal pathways. The purpose of this study is to summarize the relationship between drug resistance and glucose metabolic reprogramming in pancreatic cancer. The mechanisms and regulatory signaling pathways are also analyzed. Furthermore,the pre-clinical trials and drug development targeting the glycolysis metabolic pathways are summarized and analyzed.