Objective To observe the effects of hedysari polysaccharide (HPS) on myocardial fibrosis and the expression of MMP-2/TIMP-2 in model mice of diabetic cardiomyopathy; To discuss the mechanism of action of prevention and treatment of myocardial fibrosis in diabetes.Methods Sixty mice were randomly divided into model group, rosiglitazone group and HPS high-, mediume- and low-dose groups. The normal group was 12 non-transgenic male BKS.Cg-Dock7m+/+Leprdb/JNjumice with the same age. Each group was given relevant medicine for gavage, for 8 weeks. Blood glucose of mice before and after medication 2, 4, 6, and 8 weeks was detected. The levels of MMP-2, MMP-2 and MMP-9 in myocardium were measured by Masson staining. The protein expressions of MMP-2 and TIMP-1 in myocardium were detected by Western blot.Results Compared with the model group, the blood glucose of HPS (high- and medium dose) groups and rosiglitazone group decreased significantly. Masson staining showed that the green fibers in the model group significantly increased and rosiglitazone group and HPS high-dose group decreased compared with the model group. Western blot showed that the expressions of MMP-2 in model group and MMP-2/TIMP-2 ratio were declined significantly, while the expression of MMP-2 was increased and TIMP-2 was decreased significantly, and the ratio of MMP-2/TIMP-2 increased in rosiglitazone group and HPS high- and medium-dose group.Conclusion HPS may reduce the degree of myocardial fibrosis in model mice with diabetic cardiomyopathy. The therapeutic effect of HPS may be to relieve myocardial fibrosis in model mice by increasing the ratio of MMP-2/TIMP-2.