Objective In China, the chromium-containing Chinese traditional medicine, Tianmai Xiaoke tablet (TM), is used in the treatment of type 2 diabetes mellitus. However, its mechanism of action is not fully clear yet. The aim of this study was to investigate the effect of TM on glucose metabolism in diabetic rats and to identify whether TM has a direct effect on islet cells through microRNAs. Methods Thirty-two healthy 5-month old SPF male Sprague-Dawley rats were divided into control group, diabetic group, low dose TM group (TML), and high dose TM group (TMH). The miRNA expression profiles of pancreas samples were analyzed using microRNA array and verified by Q-PCR. Results Eight-week treatment with TM significantly decreased the fasting blood glucose in the diabetic rats. The blood glucose was significantly reduced in the TM-treated groups before and after oral glucose administration. Fasting insulin and HOMA-IR were suppressed in the TM-treated groups. miR-448, let-7b, miR-540, miR-296, miR-880, miR-200a, miR-500, miR-10b, miR-336, miR-30d, miR-208, let-7e, miR-142-5p, miR-874, miR-375, miR-879, miR-501, and miR-188 were up-regulated, while miR-301b, miR-134, and miR-652 were down-regulated in the TMH group. Through target gene analysis and real-time PCR verification, we found that these miRNAs, especially miR-375 and miR-30d, could stimulate insulin secretion of the pancreatic islets. Conclusions Our findings suggest that TM can effectively decrease FBG, enhance the sensitivity to insulin, and also modulates lipid metabolism in diabetic rats. TianMai Xiaoke Tablet may improve the blood glucose and alleviate the insulin resistance in diabetic rats through up-regulation of pancreatic miR-375 and miR-30d, promote the proliferation of islet β-cells and inhibit the proliferation of α-cells, increase the insulin gene expression, up-regulate the pancreatic let-7b, let-7e, miR-142-5p and miR-375, and suppress the function of cytokine-receptor interaction pathway and MAPK pathway.