Aim To observe the effects of alprostadil （prostaglandin E1, PGE1） on cardiac function in diabetic rats and to explore the protective effects and its mechanism. Methods 10 SD rats were selected to be normal control group from the 50 rats, and the others were given high-sugar high-fat diet for four weeks and received intraperitoneal injection of 0.1% streptozotocin to establishe diabetic rats model. Successful model rats were randomly divided into model group, PGE1 low-dose group, PGE1 middle-dose group and PGE1 high-dose group, then PGE1 low, middle, and high-dose group were respectively given 0.5, 1.0, 2.0 μg/kg alprostadil per-day intraperitoneal injection. Normal control group and model group were given an equal volume of normal saline. After treatment for 8 weeks, the following indexes of each group was measured: To detect the concentrations of serum transforming growth factor-β1 （TGF-β1）, plasma amino-terminal pro-B-type natriuretic peptide （NT-proBNP） and glycosylated hemoglobin A1 （HbA1c） To measure the collagen volume fraction （CVF） of myocardial tissue by Masson staining To detect the expressions of TGF-β1, Smad3, Smad7 proteins in myocardial tissue by Western blot. Results Compared with the control group, the concentrations of TGF-β1, NT-proBNP, HbA1c and myocardial fibrosis index CVF of model group were significantly increased, the expressions of TGF-β1 and Smad3 proteins in myocardial tissue were significantly increased, and the expression of Smad7 protein was significantly decreased （all P<0.01）. Compared with the model group, the concentrations of TGF-β1, NT-proBNP and myocardial CVF in the PGE1 middle and high-dose group were significantly reduced, the expressions of TGF-β1 and Smad3 proteins in myocardial tissue were significantly decreased, and the expression of Smad7 protein was significantly increased （all P<0.01） The changes were the most obvious in PGE1 high-dose group. There was no significant difference in each index between the PGE1 low-dose group and model group. Conclusion Alprostadil can inhibit myocardial fibrosis and improve cardiac function in diabetic rats, and the mechanism of which is related to the regulation of TGF-β1/Smad signal transduction pathway.