This study was carried out to investigate the chemopreventive effects of glycoprotein (UDN glycoprotein, 116-kDa) isolated from Ulmus davidiana Nakai on colitis-mediated colorectal cancer (CRC) in A/J mice. UDN glycoprotein intake significantly reduced the incidence and the multiplicity of colorectal tumors, induced by combination treatment with 10 mg/kg 1,2-dimethylhydrazine (DMH) and 2% dextran sodium sulfate (DSS). We found that the abnormal levels of lactate dehydrogenase (LDH), thiobarbituric acid reactive substances (TBARS), and nitric oxide (NO) were significantly suppressed in proportion to the concentration of UDN glycoprotein (0.01% and 0.02%) in the mice serum. In addition, consumption of UDN glycoprotein attenuated the activities of proliferating cell nuclear antigen (PCNA), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), and inhibited the DNA-binding activities of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) in the mice colonic tissue. Interestingly, the results obtained from reverse transcription polymerase chain reaction (RT-PCR) assay showed that 0.02% UDN glycoprotein inhibited the expressions of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mRNA in the mice. Collectively, these results suggest that UDN glycoprotein has chemopreventive activity via modulation of inflammation-related factors responsible for development of colitis-mediated CRC in A/J mice.