Abstract: To examine the hypoglycemic effects and myocardial protection of Sanghuangporus vaninii polysaccharide (SP) in T2DM rats, these effects were assessed in rats fed a high glucose and high fat diet combined with streptozotocin (STZ). The rats were randomly assigned to one of the following six groups: the diabetes mellitus (DM), metformin (MET), low-, medium-, and high-dose SP (SPL, SPM, and SPH), and control (CN) groups. Following 4 weeks of continuous intervention by gavage, the weights and multiple physiological and biochemical indicators of rats were measured and recorded, and we performed pathological observations of the pancreatic and myocardial tissues of rats.The results revealed that SP at all assessed doses can reduce weight loss in T2DM rats compared to the DM group, significantly reduce fasting blood glucose and serum insulin levels, and improve glucose tolerance (P<0.01 or P<0.05). With an increase in the dosage of SP, in serum total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels in the SP-fed rats (P<0.01 or P<0.05), whereas no significant changes in high-density lipoprotein cholesterol (HDL-C). Furthermore, there was a significant reduction in lactate dehydrogenase (LDH) activity (P<0.01), an upregulation of total superoxide dismutase (SOD) and catalase (CAT) activities (P<0.01 or P<0.05), and a significant reduction in malondialdehyde (MDA) content (P<0.01). Additionally, the SPM and SPH treatments reduced the levels of interleukin-1β (IL-1β) in rat myocardial tissues and the contents of interleukin-6 (IL-6). HE staining revealed a significant increase in the number of pancreatic islet cells in SP group rats than in the DM group rats, and the cells were more complete. Compared with the DM group, the myocardial tissue showed uniform cell gaps and reduced vacuolization after SP intervention, with the SPH group exhibiting the most significant improvement. In summary, SP can protect the structure of pancreatic and cardiac tissues, regulate blood sugar levels, reduce blood lipid contents, reduce insulin resistance, and have anti-diabetic effects in T2DM rats.