〔Abstract〕 Objective To investigate the protective effect of grape seed proanthocyanidins(GSP)on heart injury and its possible mechanism in diabetic mice. Methods Diabetic mice was induced by intraperitoneal injection of alloxan. The mice were randomly divided into model group, GSP low, middle and high dose group(65, 130, 195 mg/kg) and metformin positive control group(220 mg/kg). Meanwhile, the control group was set up. The control group and model group were given normal saline. Dynamic blood glucose, glucose tolerance and water intake were recorded during the administration.At the end of the experiment, BL-420 S was used to detect the hemodynamics of mice; the heart weight and kidney weight index were calculated; pathologicalchanges were observed by pathological staining; serological indexes were detected by enzyme-linked immunosorbent assay and colorimetry; protein expression in heart tissue was observed by immunofluorescence and western blotting. Results Compared with the control group, the blood glucose, glucose tolerance, diet and drinking water were significantly higher in the model group; the cardiac function, pathomorphology, serological indexes had changed abnormally, such as the increase of endothelin-1 A receptor(ETA) and the decrease of the endothelial nitric oxide synthase(eNOS). GSP and metformin could significantly improve the above indicators. Conclusion GSP has protective effect on heart injury in diabetic mice, and its mechanism may be related to anti-oxidant stress and improvement of endothelial dysfunction.