Aim To investigate whether the recombinant adenovirus with short chain acyl CoA dehydrogenase (SCAD) injected via tail vein can improve the vascular remodeling in spontaneously hypertensive rats (SHR). Methods The experiment was divided into 6 groups:Wistar+NS group, Wistar+GFP group, Wistar+Ad-SCAD group, SHR+NS group, SHR+GFP group and SHR+Ad-SCAD group. After purification of SCAD and GFP packed with adenovirus, the drug was injected by tail vein for 8 weeks. The cardiac function of rats was detected by echocardiography. The blood pressure changes of rats were detected by non-invasive blood pressure meter. HE staining, Sirius red staining, DHE staining, TUNEL staining, EVG staining, were used to observe the phenomenon of vascular remodeling. The expression of related proteins was detected by Western blot, and mRNA expression was detected by RT-PCR. The free fatty acid (FFA), nitric oxide (NO) content and ATP content were observed. Results (1) After SCAD recombinant adenovirus was injected via tail vein, the expression of SCAD protein was significantly upregulated in the aorta of rats, meanwhile, the mRNA level was observably increased, and the activity of SCAD was markedly increased. (2) In the pathological state of rats, the rising of SCAD can lower blood pressure, improve heart function and vascular lumen size, reduce collagen deposition, result a poor production of vascular ROS, consequently, give lower to apoptosis. (3) Under pathological conditions, overexpression of SCAD can reduce FFA content of serum and aorta, increase the ATP level in aorta, activate eNOS phosphorylation, increase NO production in aorta. Conclusion The upregulation of SCAD in aorta of SHR can reverse hypertensive vascular remodeling, which may be related to decreasing FFA content of serum, increasing NO levels, reducing ROS production and eliminating oxidative stress.