Angiotensin II (angII), a key effector of the renin-angiotensin-aldosterone system (RAAS), is an important mediator of pathological cardiac and vascular changes by contributing to cardiac hypertrophy and altered vascular tone, inflammatory processes and structural remodeling with fibrosis. Calcineurin (PPP3), a serine/threonine protein phosphatase consisting of an enzymatic and a catalytic subunit, is known for its role in inflammatory processes and cellular hypertrophy. One of its ubiquitously expressed enzymatic subunits, PPP3CB, has been shown to influence T cell development and also angII-induced cardiac hypertrophy [1, 2]. To investigate the role of PPP3CB for vascular changes stimulated by angII, we analysed the effect of a global PPP3CB knockout (KO) on the murine aorta. Under basal conditions, no upregulation of the PPP3CA subunit due to PPP3CB KO was detectable excluding a compensatory effect in adult male mice. Additionally, KO animals had no obvious phenotype under basal conditions compared to wildtype (WT) littermates. Contractility of aortic rings from PPP3CB WT and KO mice was measured via mulvany wire myography and was not altered after acute angII-receptor activation, indicating normal functionality under these conditions. Additionally, endothelium-dependent relaxation mediated by carbachol and SNAP showed no significant difference excluding an endothelial dysfunction. Subsequently, angII was applied chronically for 28 days (500ng/kg/day) to mice by subcutaneous implantation of osmotic minipumps (surgery under isoflurane anesthesia (2%, 1 L/min O2)) and systolic blood pressure was measured via tailcuff. In PPP3CB KO mice, angII-induced systolic blood pressure increase was smaller than in WT mice. In histological stainings, KO mice showed less aortic wall thickening after angII treatment and an increase in lumen area compared to WT mice was detectable. Aortic gene expression, assessed by Next Generation Sequencing, was significantly altered in angII-treated WT mice with an upregulation of fibrosis related genes (COL1a1, CTGF) inflammation markers (PAI-1) and adhesion related genes (ACAN, FN-1) compared to KO animals. A slight difference in collagen I and fibronectin-1 secretion upon angII-stimulation, analysed with ELISA in freshly isolated aortic vascular smooth muscle cells (aVSMCs) of WT and KO animals, revealed a possible involvement of aVSMCs in the observed angII-induced vascular changes. Overall, our results suggest that the pathological effects of angII in the vasculature are partially mediated by PPP3CB. While the acute effects of angII on vascular tone are not affected by PPP3CB, chronic vascular remodeling and blood pressure is reduced in PPP3CB KO mice compared to WT controls.