Background. Liver Growth Factor (LGF) is a liver mitogen with antifibrotic and regenerative properties in several biological systems, including liver, nervous, reproductive and respiratory system (1, 2). Our previous study in spontaneously hypertensive rats (SHR) demonstrates that a short treatment with LGF (4.5 micro grams LGF/rat, i.p., twice a week during 2 weeks) exerts antihypertensive effects, improving large artery composition and function (3). Resistance arteries play a key role in the regulation of blood pressure and in SHR resistance artery remodelling and stiffening participates in the development and maintenance of hypertension. Our aim has been to determine if the antihypertensive actions of LGF in SHR are partially due to improvement of the resistance vasculature. Methods. 3ther order Mesenteric Resistance Arteries (MRA) from adult male SHR, WKY and SHR treated with LGF were used. MRAs were mounted on a pressure myography to study vascular structure and mechanics. Thereafter, MRAs were pressure-fixed with 4% PFA at 70 mm Hg and stained with the nuclear dye DAPI. Intact arteries were mounted on a slide provided with a well to avoid vessel compression and visualized with confocal microscopy at 364m (DAPI) and 488nm (autofluorescence of elastin) to determine cellular distribution and elastin organization. Images were analyzed with Metamorph Image Analysis Software. Results. As previously described SHR MRA showed eutrophic inward remodelling and stiffening, when compared to WKY vessels. LGF treatment did not modify vascular structure but improved distensibility and reduce intrinsic stiffness. Detailed analysis of the structure of the different layers of the vascular wall showed that SHR arteries exhibited a reduction of the volume of the media occupied by Smooth Muscle Cells (SMC) with no change in adventitial cell or endothelial cell density. The relative area occupied by elastin in the internal elastic lamina was significantly larger in SHR arteries compared to WKY, due to a reduction in the size of fenestrae. LGF increased SMC and endothelial cell density, with no change in the adventitia and reduced the area occupied by elastin increasing fenestrae number without modification of size. Conclusions. Short LGF treatment of SHR rats improves wall composition by increasing SMC number and reducing extracellular matrix. These changes reduce the vascular stiffening characteristic of SHR resistance vessels and might participate in the hypotensive effects of LGF treatment in SHR rats.