Fine tuning of Na ⁺ reabsorption takes place along the aldosterone-sensitive distal nephron (ASDN) which includes the collecting duct (CD) where it is mainly regulated by aldosterone. In the CD,Na ⁺ reabsorption is mediated by the epithelial sodium channel (ENaC) and the sodium pump (Na,K-ATPase). Paracellular ion permeability is mainly dependent on tight junction permeability. Claudin-8 is one of the main tight-junction proteins expressed along the ASDN. We have previously shown a coupling between trancellular Na ⁺ reabsorption and paracellular Na ⁺ barrier. We hypothesize that aldosterone controls the expression levels of both transcellular Na ⁺ transporters and paracellular claudin-8 in a coordinated manner. Here, we show that aldosterone increased mRNA and protein levels as well as lateral membrane localization of claudin-8 in cultured CD principal cells. The increase in claudin-8 mRNA levels in response to aldosterone was prevented by preincubation with 17-hydroxy progesterone, a mineralocorticoid receptor antagonist, and by inhibition of transcription with actinomycin D. We also show that low salt diet which stimulated aldosterone secretion was associated with increased claudin-8 abundance in the mouse kidney. Reciprocally, mice subjected to high salt diet which inhibits aldosterone secretion or treated with spironolactone, a mineralocorticoid receptor (MR)antagonist, displayed decreased claudin-8 expression. Inhibition of glycogen synthase kinase-3 (GSK3), Lyn and Abl signaling pathways prevented the effect of aldosterone on claudin-8 mRNA and protein abundance, suggesting that signaling protein kinases plays a permissive role on the transcriptional activity of the mineralocorticoid receptor.This study shows that signaling via multiple protein kinases working in concert mediates the aldosterone-induced claudin-8 expression in collecting duct.