Background and Aims. Although the differential expression of microRNA (miRNA) genes has been identified in many diseases, little information exists concerning the miRNA expression profile in type 2 diabetes mellitus (T2DM) with diarrhea-predominant irritable bowel syndrome (D-IBS). Therefore, the specific expression of miRNAs in diabetes with D-IBS is identified in the study. Materials and Methods. 201 patients with IBS and 220 matched healthy controls were included in the study. Microarray technology and real-time reverse transcriptase-polymerase chain reaction analysis (RT-PCR) were taken to examine the miRNA expression profiles of T2DM patients with diarrhea-predominant irritable bowel syndrome (D-IBS) compared with patients with T2DM, patients with D-IBS, and control subjects. Results. We have found that 35 miRNAs were differentially expressed in T2DM with D-IBS, in which three representative miRNAs, hsa-miR-106b, hsa-miR-26a, and hsa-miR-29b, were found to be significantly elevated in T2DM with D-IBS by RT-PCR. Conclusions. Our study has indicated that hsa-miR-106b, hsa-miR-26a, and hsa-miR-29b were elevated in T2DM with D-IBS, which may be the potential biomarkers of T2DM with D-IBS. To obtain a better understanding of the biological functions of these miRNAs in T2DM with D-IBS, functional annotation analysis suggested that the MAPK pathway may be responsible for T2DM with D-IBS.