Objective To investigate metabolomic changes in the serum of rats with persistent hypertensive SHR and reveal the possible pathogenesis. Methods Six male SHR and six WKY rats were selected at random and defined as the model group and the control group. Rats were given 120 d standard feeding and rat SBP was measured using the BP2000 platform once a week. Rat myocardial tissue was stained with HE and Masson staining and rat serum was detected by UPLC- MS to identify significant metabolites. In addition, a GO and KEGG pathway enrichment analysis was performed. Results The SBP of the model group gradually increased and peaked at aged 20 weeks, which was followed by a plateau period. The SBP of SHR at all time points was much higher than that of the control group (P< 0. 001). HE staining showed that the myocardial tissue of the model group was in a disordered arrangement, and the vessel walls were thicker, while their lumen was narrower. Homogeneous, pink-colored substances were largely found in both the myocardium and around the lumen. Masson staining revealed a very large amount of collagen fiber accumulated in the myocardium of the model group. The serum metabolic patterns and individual differential metabolites of the two groups were evidently separated from each other, and a total of 44 potential landmark metabolites were finally identified, mainly involving neuroactive ligand-receptor interactions, 5-hydroxytryptamine receptors, and arachidonic acid metabolism pathways. Conclusions Myocardial and perivascular fibrosis were identified in SHRs under long-term hypertension. Serum metabolomics of SHR obviously deviated from the normal metabolic pattern, and significant metabolites were primarily involved in regulating vasoconstriction and vasodilation, modulating the activity of the sympathetic nerve, and inhibiting the inflammatory response.