As a nuclear receptor, peroxisome proliferator-activated receptor-δ (PPARδ) plays a critical role in regulating inflammation and cancer, while it is still unclear the mechanism of PPARδ agonist GW501516 on colitis-associated colorectal cancer. Here we found that GW501516 significantly enhanced colitis-associated colorectal cancer in AOM/DSS-induced mice. In addition, PPARδ agonist GW501516 enhanced pro-inflammatory gene expressions (COX-2, IL-6, IL-8 and MCP-1) in inflamed colon. Further analysis showed that GW501516 increased the expressions of Glut1 and SLC1A5 in colon cancer cells as well as AOM/DSS-induced colorectal tumors. These findings revealed a new mechanism of PPARδ agonist GW501516-mediated colitis-associated colorectal cancer.