Considering the increased colon cancer risk associated with chronic colitis, we have therefore examined the effects of long-acting hGly(2)GLP-2, as well as of endogenous GLP-2 using the antagonist hGLP-2(3-33) in two novel models of inflammation-associated colon cancer: rats fed the carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and a high-fat diet (HFD) for one or three cycles, and mice with chronic dextran sodium-sulfate (DSS)-induced colitis administered AOM. hGly(2)GLP-2 treatment of one-cycle PhIP/HFD rats increased the number of colonic aberrant crypt foci by 72 ± 11% (P < 0.01).