Exposure to environmental pollutants such as PolyChlorinated Biphenyls (PCBs) is now taken into account to partly explain the worldwide decline of amphibians. PCBs induce deleterious effects on developing amphibians including deformities and delays in metamorphosis. However, the molecular mechanisms by which they express their toxicity during the development of tadpoles are still largely unknown. A proteomic analysis was performed on developing Xenopus laevis tadpoles exposed from 2 to 5 days postfertilization to either 0.1 or 1 ppm of the PCBs mixture Aroclor 1254. Two dimensional in gel electrophoresis (2D-DIGE) with minimal labelling method coupled to nano flow liquid chromatography tandem mass-spectrometry were used to detect and identify proteins differentially expressed under PCBs conditions. Results showed that 59 spots from the 0.1 ppm Aroclor 1254 condition, and 57 spots from the 1 ppm Aroclor 1254 condition displayed a significant increase or decrease of abundance compared to the control. In total, 28 proteins were identified. The results suggest that PCBs induce mechanisms against oxidative stress (peroxiredoxins 1 and 2), adaptative changes in the energetic metabolism (enolase 1, glycerol-3-phosphate dehydrogenase, creatine kinase M and B type), and the implication of the Unfolded Protein Response system (glucose regulated protein 58 kDa). They also affect, at least at the highest concentration tested, the synthesis of proteins involved in normal cytogenesis (alpha-tropomyosin, myosin heavy chain, alpha-actin,.). For the first time, proteins such as aldehyde dehydrogenase 7A1, CArG binding factor-A, prolyl 4-hydroxylase beta and nuclear matrix protein 200 were also shown to be upregulated by PCBs in developing amphibians. These data argue that protein expression reorganization should be taken into account while estimating the toxicological hazard of wild amphibian populations exposed to PCBs.