Renal fibrosis, particularly tubulointerstitial fibrosis, is the common final outcome of almost all chronic kidney diseases. However, the mechanisms involved in the development of renal fibrosis are poorly understood. The Akt (also known as protein kinase B, PKB) family is serine/threonine protein kinases that play critical roles in regulating growth, proliferation, survival, metabolism and other cellular activities. Cytokines, high-glucose medium, transforming growth factor-beta 1 or advanced glycation end-products activate Akt in different renal cells. Increased Akt activation has been found in experimental tubulointerstitial fibrosis. In addition, Akt activation is also an important node in diverse signaling cascades involved in kidney damage. These data give evidence for a role for Akt in renal fibrosis, but no reviews are available on the role of Akt in the process. Thus, our aim is to review the role of Akt activation and signaling in renal fibrosis.