Manual acupuncture (MA) can be used to manage high blood pressure; however, the underlying molecular mechanism remains unknown. To explore the mechanism of acupuncture in the treatment of hypertension, Wistar Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) were subjected to either MA stimulation or the corresponding sham procedure as a negative control (Sham-MA) for 1 week. PET-CT scans, transcriptomics and molecular biology were used to evaluate the effect of MA. The results show that MA can regulate blood pressure in SHRs, change the glucose metabolism of the paraventricular hypothalamus (PVH), and affect the mRNA and protein expression levels of differentially expressed genes in the PVH. These genes may lower blood pressure by regulating angiotensin, endothelial function and inflammation. These findings reveal that MA regulates multiple biological processes and genes/proteins of the PVH, and provide a solid theoretical basis for exploring the mechanisms by which MA regulates hypertension.