To investigate the differential expression of microRNA (miRNA) in colon between ulcerative colitis (UC) and ulcerative colitis related colorectal cancer (UCRCC). An UC mouse model was built by dextran sodium sulfate, and an UCRCC mouse model by dextran sodium sulfate and 1,2-diformylhydrazine. RNAs were extracted from the colon, purified and hybridized with fluorescence-labeled miRNA oligonucleotide gene chip. Real-time fluorescence quantitative PCR was used to verify the expression variation of miRNA. SAM was employed for the data analysis. The up-regulated miRNAs in colon cancer included has-miR-194, has-miR-215, has-miR-93, has-miR-192, has-miR-92a, has-miR-29b, and has-miR-20a (median false discovery rate<5%), while the down-regulated miRNAs were has-miR-1231, has-miR-195, has-miR-143, and has-miR-145 (median false discovery rate<5%). Significant differential expression of miRNA was found between the UC mouse and UCRCC mouse, which may be related to the onset, erosion and transfer of colorectal cancer.