Aim To evaluate the effect of sphingosine-1-phosphate (S1P) receptor agonist FTY720 on early diabetic rat myocardial microvascular lesions. Methods Male Spragure-Dawley (SD) rats were divided into three groups:normal control group, diabetic model group, FTY720-treated group (0.001 g/kg per day orally). Diabetic model rats received intraperitoneal injection of streptozotocin (65 mg/kg). The heart tissue structure was estimated by HE staining. The myocardial microvessel density was observed by CD34 immunohistochemistry. The cardiac microvascular endothelial cell apoptosis was analysed by TUNEL and immunofluorescence mapping. Immunohistochemical staining for TGF-β and typeⅠcollagen were observed with respect to collagen content. Western blot analysis was used to investigate VCAM-1, TNF-α, and IL-6 protein expression. Results Multiple random blood glucose≥16.7 mmol/L was as a marker of diabetic model. In this study, the success rate of diabetic rat model was above 85%. Compared with the normal control group, diabetic model rat myocardial microvascular wall was thickened, the expression of VCAM-1, TNF-α and IL-6 was higher (P＜0.05). The expression of VCAM-1, TNF-α and IL-6 in FTY720-treated group was significantly lower than those in diabetic model group (P＜0.05). In diabetic model group, the density of vascular endothelial cells was decreased and the apoptotic index was significantly increased, while FTY720 could reduce the apoptosis and promote the proliferation of endothelial cells. Conclusion FTY720 may play a protective role in myocardial microvascular injury in diabetic rats.