Mineralocorticoids stimulate renal tubular Na+ reabsorption, enhance salt appetite, increase blood pressure (BP) and favour the development of renal fibrosis. The effects of mineralocorticoids on renal tubular Na+ reabsorption and salt appetite involve the serum- and glucocorticoid-inducible kinase 1 (SGK1). The present experiments explored the involvement of SGK1 in DOCA induced renal fibrosis. To this end SGK1-knockout mice (sgk1-/-) and their wild type littermates (sgk1+/+) were implanted with DOCA release pellets and offered 1 % saline as drinking water for 12 weeks. The treatment led to significant increases in fluid and Na+ intake, and urinary output of fluid and Na+ in sgk1+/+ mice, effects blunted in sgk1-/- mice. BP increased within the first 7 weeks to a similar extent in both genotypes but within the next 5 weeks increased further only in sgk1+/+ mice. DOCA led to marked albuminuria in sgk1+/+ mice, an effect significantly blunted in sgk1-/- mice. Histology after 12 weeks treatment revealed marked tubulointerstitial fibrosis in kidneys from sgk1+/+ mice but not from sgk1-/- mice. In conclusion, lack of SGK1 protects against DOCA/high salt induced proteinuria and renal fibrosis.