Previous studies (Vaidya et al 2003, Korrapati et al 2005; 2006) demonstrated that renal repair stimulated by a low dose of S-(1,2-dichlorovinyl)-L-cysteine (DCVC) (15 mg/kg, ip) 72 h before administration of a normally lethal dose (75 mg/kg, ip), protects mice from acute renal failure (ARF) and death (autoprotection). Present study identified the proteins indicative of DCVC-induced ARF and autoprotection in male SW mice. Renal dysfunction and injury were assessed by plasma creatinine and histopathology, respectively. Whole kidney homogenates were run on 2-DE gels and expression of 18 common proteins was maximally changed (± 10 fold) in all the treatment groups, and were conclusively identified by LC-MS/MS. These proteins were mildly down-regulated after low dose alone and in autoprotected mice in contrast to severe down-regulation with high dose alone. Glucose regulated protein 75 (GRP75) and proteasome subunit type 1 (PSA1) were further investigated for their localization in the kidneys of all the groups by immunohistochemistry. These proteins were substantially higher in the proximal convoluted tubular epithelial cells in the low dose and autoprotected groups when compared to high dose alone group. Proteins involved in energetics were down-regulated in all the three groups of mice leading to a compromise in cellular energy. However, energy is completely recovered in low dose and autoprotected mice. This study provides the first report on protein profiling in DCVC-induced ARF and autoprotection in mice and reflect the application of proteomics in mechanistic studies as well as biomarker development in a variety of toxicologic paradigms.