Hypertension is a common cardiovascular disease in clinical scenario. The level of leptin changes with the development of hypertension and is regulated by Aldehyde dehydrogenase2 (ALDH2). Our study explored the relationship between irbesartan treatment and ALDH2. Spontaneously hypertensive rats were treated with irbesartan solution and ALDH2 over expression adenovirus vector for experimental group, and the equivalent amount of spontaneously hypertensive rats was treated with irbesartan solution and null adenovirus vector for control group. Sham group included spontaneously hypertensive rats treated with saline solution and null adenovirus vector. Pathological change of cardiac muscle tissue was observed with microscope. N-terminal Pro-brain natriuretic peptide, blood pressure, left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS) and renal function were assessed to determine cardiovascular function. Expression of serum leptin and mRNA of leptin were examined, respectively. ALDH2 was confirmed by western blot examination. Statistical Analysis was performed to determine correlation. Compared with sham group, ALDH2 were decreased significantly in control group. Remarkable pathological changes of cardiovascular and renal injury were observed in control group rats, including increased NT-proBNP, renal interstitial fibrosis and aberrant hypertension. Compared with control group, experimental group had lower levels of blood pressure and NT-proBNP, but higher level of Glomerular Filtration Rate (GFR). Moreover, irbesartan -treated rats had significantly higher levels of leptin, suggesting irbesartan treatment ameliorated symptoms of hypertension. Expression of serum leptin had a negative correlation with mRNA of leptin (P<0.05). Moreover, compared with control group, ALDH2 over expression significantly improved irbesartan treatment, verified by hypertension related index. Decreased ALDH2 expression were correlated with progression of hypertension. Rats with Hypertension indeed benefited from irbesartan treatment. ALDH2 elevated the drug susceptibility of irbesartan treatment for hypertension via regulating serum leptin, and improved efficacy of irbesartan treatment on hypertension.