Objectives: To determine the effects of a 7-day diet with high salt (HS) on the level of inflammation and balance of Th17 and Treg lymphocytes in healthy young subjects, and to examine the association of inflammatory response due to a 7-day HS with previously proven functional impairment of microvascular reactivity and increased oxidative stress. Study design: The study was designed as a non-randomized controlled trial, in which all subjects underwent the same experimental protocol with multiple repeated measurements. Participants and methods: The study involved 30 young, healthy subjects who were put on a low salt diet for 7 days (LS, ~ 3.5 g salt/day) and after that all subjects were on a HS diet (~ 14.7 g salt/day) for a period of 7 days. Before and after the 7-day HS diet, the following were measured: a) serum proinflammatory and antiinflammatory cytokines; b) markers of endothelial activation (sICAM-1, sVCAM-1, E-selectin, endoglin); c) frequency of Th17 and Treg cells; d) levels of enzymes involved in the differentiation of Th17 and Treg cells (SGK1 and p38MAPK); e) markers of oxidative stress and antioxidant capacity (TBARS, 8-iso-PGF2α, FRAP); and f) microvascular reactivity in response to vascular occlusion (PORH) and acetylcholine iontophoresis (AChID) by laser Doppler flowmetry (LDF). Results: The HS diet significantly increased serum levels of proinflammatory cytokines IFN-γ, TNF-α, IL-9, and IL-17A, but also of anti-inflammatory cytokines IL-10 and TGF-β1. The relative amount of SGK1 increased significantly after the HS diet. The HS diet significantly increased TBARS and 8-iso-PGF2α, and decreased FRAP. PORH and AChID were significantly reduced after the HS diet. Increased levels of oxidative stress after HS diet were negatively associated with Treg cell frequency, while there was a positive association between IL-10 and PORH. Conclusion: Increased levels of proinflammatory and anti-inflammatory cytokines after HS indicate that the HS diet elicits an early proinflammatory response, but also an anti-inflammatory response mediated by Treg cells in salt resistant young individuals. The obtained results support the role of the IL-23/SGK1/Th17cell/IL-17A axis in the immune response during HS loading in healthy individuals. HS diet has led to an increase in the markers of oxidative stress and a decrease in antioxidant capacity and a decrease in endothelium-dependent dilatation in the skin microcirculation. There is a possibility that oxidative stress alters immune regulatory mechanisms by acting on Treg cells, and that a favorable anti-inflammatory milieu is important for maintaining normal endothelial function.