Objectives: To understand the underlying mechanisms of CNI-induced renal vascular injury and hypertension. Methods: Changes in mouse arterial blood pressure (BP) were monitored under anesthesia via a pressure transducer attached to a carotid artery cannula. BP in conscious mice was measured by a noninvasive tail-cuff system. Microperfusion was used to assess the contractile and dilatory function of renal afferent arterioles (Af-Art). Results: Long-term administration of Tac lead to the activation of renin-angiotensin system (RAS). Tac-induced vascular remodeling of renal arterioles could be rescued by valsartan, an AT1R inhibitor. In mice treated with Tac, vasoconstriction in response to angiotensin II was markedly enhanced , which was abolished by valsartan. Notably, the expression of senescence-related biomarkers was upregulated in mesenteric and renal resistance arteries from Tac-treated mice. However, Tac co-administration with valsartan or ABT-263, a senolytic agent, rescued Tac-induced vascular injury and hypertension. Moreover, valsartan and ABT-263 also alleviated Tac or Ang II induced cellular senescence in vitro. Conclusions: Long-term administration of Tac induces renal vascular injury and hypertension, which is rescued by valsartan, possibly via the inhibition of cellular senescence.