ObjectiveTo observe the regulatory effect of Yuyetang on Ghrelin level in rats with type 2 diabetes mellitus （T2DM）-induced cognitive impairment （DCI） and explore the pathway in the prevention and treatment of DCI. MethodThe T2DM model was induced in rats by intraperitoneal injection of streptozotocin （STZ） combined with the high-fat and high-sugar diet （STZ）. The model rats were divided into model group， metformin group （200 mg·kg^-1）， and low-，medium-， and high-dose Yuyetang groups（4.575，9.15， 18.3 g·kg^-1）according to the blood glucose， with 10 rats in each group. A normal group was also set up. The rats were administered with corresponding drugs by gavage for 30 days， and the body weight and blood glucose of the rats in each group were observed and recorded. After drug intervention， the learning and memory abilities of rats were tested by the Morris water maze. After the test， the whole brains of rats were sampled for hematoxylin-eosin （HE） staining to observe the pathological changes in the hippocampal CA1 region， and the expression of Ghrelin in gastric tissues and hippocampal CA1 region was detected by immunohistochemistry. ResultCompared with the normal group ， the model group showed increased blood glucose（P<0.01），reduced body weight（P<0.01），prolonged escape latency（P<0.05，P<0.01）， shortened retention time and movement distance in the target area，decreased number of platform crossings（P<0.01）， abnormal morphology and structure of cells with disordered arrangement and reduced number in the hippocampal CA1 region， and decreased expression of Ghrelin in the serum，hippocampal CA1 region， and gastric tissues（P<0.05， P<0.01）. Compared with the model group， the medium- and high-dose Yuyetang groups showed increased body weight， while all Yuyetang groups showed reduced blood glucose（P<0.01）， shortened escape latency （P<0.05）， prolonged retention time and movement distance in the target area，increased platform crossings （P<0.05， P<0.01）， improved morphology and structure of cells， increased number of normal cell in the hippocampal CA1 region， and elevated Ghrelin levels in the serum， gastric tissues， and hippocampal CA1 region（P<0.05， P<0.01）. ConclusionYuyetang can effectively improve the cognitive ability of DCI rats， and its mechanism may be related to the regulation of Ghrelin levels in the serum， hippocampal CA1 region， and gastric tissues.