BACKGROUND Diabetes is a risk factor for coronary atherosclerosis and coronary heart disease. Resveratrol (RESV) is a natural compound with anti-inflammatory effects. The objective of this study is to evaluate the cardio protective effects of RESV in a diabetic rat model with coronary heart disease. MATERIAL AND METHODS Diabetic rat model with coronary heart disease was constructed by feeding high-fat and high-calorie diet, followed by injection of streptozotocin. The diabetic rats received RESV or DMSO as treatment. Insulin, total cholesterol, and total triglyceride levels in serum were measured using enzyme-linked immunosorbent assay (ELISA) to evaluate the effect of RESV in alleviating diabetic symptoms. Inflammatory factors, including tumor necrotic factor α, interleukin-6, interleukin-8, intracellular adhesion molecule 1, vascular-cell adhesion molecule 1, and monocyte chemoattractant protein-1 were assayed using ELISA. Real-time polymerase chain reaction and western blot analysis were performed to evaluate the impact of RESV treatment on the TLR4/MyD88/NF-κB signaling pathway (toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa B signaling pathway). Hematoxylin and eosin staining was used to document pathological changes in cardiovascular muscles. RESULTS RESV preserved pancreatic tissue, which therefore reduced levels of glucose and triglycerides glyceride in serum. Inflammatory factors were also suppressed by RESV. TLR4/MyD88/NF-κB signaling pathway was downregulated after RESV treatment. CONCLUSIONS RESV offers protective effects of cardiovascular tissues in the diabetic rat model with coronary heart disease. Those effects are mediated by downregulating the TLR4/MyD88/NF-κB signaling pathway.