<b><i>Background/Aims:</i></b> Chronic kidney disease (CKD) is associated with large artery remodeling, endothelial dysfunction and calcification, with angiotensin II (Ang II) a known driver of these pathologies. We investigated long-term Ang II type 1 receptor inhibition with valsartan on aortic function and structure in the Lewis polycystic kidney (LPK) rat model of CKD. <b><i>Methods:</i></b> Mixed sex LPK and Lewis control (total <i>n</i> = 28) treated (valsartan 60 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups were studied. Functional responses to noradrenaline (NA), potassium chloride and endothelium-dependent and independent relaxations were investigated in vitro using acetylcholine hydrochloride (ACh) and sodium nitroprusside (SNP), respectively. Effects of the nitric oxide synthase (NOS) substrate <smlcap>L</smlcap>-arginine, NOS inhibitor <smlcap>L</smlcap>-NAME and cyclooxygenase inhibitor indomethacin on ACh responses were examined. <b><i>Results:</i></b> In the LPK, valsartan reduced systolic blood pressure and urinary protein, ameliorated exaggerated sensitivity to NA, and normalized endothelium-dependent (ACh-R_max; 91 ± 7 vs. 59 ± 6%, <i>p</i> = 0.0001) and independent dysfunction (SNP-R_max; 99 ± 1 vs. 82 ± 7%, <i>p</i> = 0.040), as well as improving NO-dependent relaxation (R_max; -51 ± 6 vs. -26 ± 9%, <i>p</i> = 0.008). Valsartan also reduced aortic wall hypertrophy, elastin disruption/fragmentation, calcification, media cystic degeneration, and levels of matrix metalloproteinase 9. <b><i>Conclusions:</i></b> This study highlights the role of Ang II in driving vascular manifestations of CKD and indicates that early treatment can significantly limit pathological changes.