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The purpose of this research was the identification of potential dose-dependent and time-dependent serum protein biomarkers of low level kidney degradation in a rat model. Potential biomarkers were evaluated based on differential protein expression between control and dosed samples in rat serum. Proteins of interest demonstrated upregulation at a minimum 1.5 fold increase in protein concentration control versus dosed sample. In order to identify common biomarkers of kidney decrement, three nephrotoxins were chosen to target specific locations of the kidney: 1) D-Serine, which causes necrosis of the proximal straight tubules, 2) Puromycin, an antibiotic that degrades the Glomerular Basement Membrane (GBM), and 3) Bromoethyl Amine (BEA), which affects the proximal tubules as well. Rats were dosed with individual neprotoxins and serum collected at Pre-dose, 24 hrs Post dose, and at terminal sacrifice for Puromycin andBEA, and at 12 hrs and 24 hrs post-dose from d-serine. The collected serum sample was enriched to remove abundant proteins, separated using 2D Difference in Gel Electrophoresis (DIGE), and screened for potential up-regulated biomarkers based on difference in fluorescent intensity using computer software. Finally, the proteins were trypsin digested and the resultant peptides identified by MALDI-TOF/TOF mass spectroscopy. The study results indicated hornerin as a potential biomarker though no dose- or time-dependent toxicity could be determined.