Background Schisandra chinensis (S. chinensis) is a drug commonly used in the clinical treatment of cardiovascular diseases in Traditional Chinese Medicine. However, the specific components and mechanisms of its action are still unclear. We screened six kinds of lignans from S. chinensis with high content and found that schisandrol A and schisantherin A had a strong vasorelaxant effect. The purpose of this study was to investigate the relaxation and underlying mechanism of schisandrol A in the isolated thoracic aorta of rats. Materials and Methods Isolated rat endothelium-intact and endothelium-removed thoracic aorta strips were pre-constricted with phenylephrine (PE), and the relaxation of schisandrol A on the strips was observed. Then, the mechanism was explored by pre-incubating the strips with nitric oxide synthetase inhibitor Nɷ-nitro-l-arginine methyl ester (L-NAME), cyclooxygenase inhibitor (indomethacin), potassium channel blockers 4-aminopyridine (4-AP), barium chloride (BaCl2), tetraethylamine (TEA), and glibenclamide, respectively, and changing the calcium concentration in the bath. In addition, expressions of endothelial nitric oxide synthetase (eNOS) mRNA and protein in rat thoracic aorta were detected. Results Schisandrol A induced both endothelium-dependent and endothelium-independent relaxation of isolated thoracic aorta strips of rats, and the mechanism might be related to promoting the synthesis of NO, inhibiting Ca2+ release from the sarcoplasmic reticulum, and blocking the Ca2+ channels. Conclusion These discoveries may provide a theoretical basis for the traditional application of S. chinensis to treat cardiovascular disease.