In the area of medicine food homology, Myrica rubra ((Lour.) Siebold & Zucc.) has been used in medicine as an astringent and anti-diarrheal. However, there are few in-depth studies evaluating the antihypertensive chemical components and antihypertensive mechanisms of Myrica rubra . Thus, the aim in this study was to assess the protective effects of an ethanol extract of bayberry (BE) on spontaneous hypertension in rats. In this study, liquid chromatography-mass spectroscopy (LC-MS) coupled with biochemical assays and western blot have been employed to study the protective effects of BE against hypertension. A total of 28 compounds were identified in BE. According to this study, treatment with BE (2 g kg -1 ) resulted in the potent and persistent reduction of high blood pressure, even after drug withdrawal. The results indicate that the mechanisms of action might involve protection against damage to the vascular structure. Bayberry extract could enhance the endothelium-independent vascular function, inhibiting the abnormal proliferation of smooth muscle by inhibition of glucose transporter-1 (GLUT 1) and regulation of nitric oxide (NO)/serine/threonine kinases (Akt)/endothelial nitric oxide synthase (eNOS). The results of molecular docking and in vitro research indicated six compounds in BE that might be responsible for the antihypertensive effect attributed to GLUT 1, eNOS and Akt, and further in vivo studies are needed to verify this.