BACKGROUND: The increasing incidence of diabetes mellitus (DM) is of great clinical significance. In this study, we aimed to investigate whether exposure of endothelium-intact aortic rings to simvastatin could have a vasorelaxant effect in diabetic rats. METHODS: For induction of diabetes, streptozotocin (STZ) (60 mg/kg, i.p., single dose) was used. After 1 month, the cumulative reaction of isolated endothelium-intact aortic rings was determined to KCl and phenylephrine (PE) in the absence and presence of nitric oxide (NO) synthase inhibitor, i.e., nitro-L-arginine-methyl ester (L-NAME), and prostaglandin synthesis inhibitor, i.e., indomethacin. Meanwhile, the role of extracellular calcium was assessed in this respect. RESULTS: At the end of the study, the addition of simvastatin (at a concentration ≥ 10−5 M) caused a significant concentration-dependent relaxation response of PE-precontracted aortic rings for both control and diabetic groups (at a significant difference of P < 0.050), and this difference did not exist for KCl-precontracted aortic rings. Furthermore, both L-NAME (100 µM) and indomethacin (10 µM) significantly diminished the vasorelaxant response following simvastatin addition. Meanwhile, there was no statistically significant difference between control and diabetic groups in the absence of extracellular calcium. CONCLUSION: The results of this study suggest that simvastatin is able to relax PE-precontracted aortic rings isolated from STZ-diabetic rats via modulation of NO- and prostaglandin-dependent signaling and its effect is not via modulation of calcium mobilization from intracellular stores.