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We have established rat models of pancreatic ductal adenocarcinoma (PDAC) in which expression of a human H-rasG12V or K-rasG12V oncogene regulated by the Cre/lox system drives pancreatic carcinogenesis. Pancreatic ductal adenocarcinoma which develops in H-rasG12V and K-rasG12V transgenic rats is cytogenetically and histopathologically similar to human PDAC. The present study was designed to determine the feasibility of using the commercially available H-rasG12V transgenic rat to find diagnostic protein biomarkers for human pancreatic cancer.For an animal model to be useful for searching for protein biomarkers for a disease, it is essential that proteins that are up-regulated in the model are also up-regulated in humans. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to compare H-rasG12V transgenic rat PDAC with surrounding normal pancreas tissue.We identified 30 up-regulated proteins in the H-rasG12V transgenic rat PDAC lesions; importantly, 21 human homologs of these 30 rat proteins are up-regulated in human pancreatic cancer patients.These results indicate that numerous proteins that are up-regulated in H—rasG12V transgenic rat PDAC are also up-regulated in human pancreatic cancer; therefore, this rat model can be used to search for diagnostic biomarkers for this disease.