Acrylamide in drinking water was administrated to the C57BL/6 male mice at different concentrations during a nine week experimental period. The main objective was to utilize the proteomics tools like the SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional gel electrophoresis (2DE) to study the proteomics of liver upon acrylamide intoxication been liver the major site of acrylamide metabolism and detoxification. However, the mice general health including blood parameters, weight changes and liver gross appearance were also investigated. The data were analysed and correlated with different acrylamide concentrations throughout the experimental period. The results from both control and the experimental mice were compared to analyse the effect of acrylamide on the experimental mice. Overall the acrylamide at different concentrations used in this study (0, 0.5, 5, 50, and 500 ug acrylamide/kg,) did not have a significant effect on the general health of the mice and both the controls and the experimental had little effect on general physiological conditions. It appeared that the experimental mice tolerated the specific concentrations used in this study and perhaps the acrylamide was not enough to cause any major side effect. However, the proteomic studies of the liver have clearly shown that the protein expression is effected by ingestion of acrylamide in drinking water. While the SDS-PAGE pattern of liver proteins showed minimal variations, analysis of the 2-D gel maps of the controls and lowest acrylamide treatment group using the Image Master software has reported at least 10 proteins which founded to be significantly affected (T > 2) by the acrylamide treatment. Five proteins were possibly identified using the ExPASy server of the SWISS-2DPAGE database. The affected proteins were up-regulated or down-regulated depending on their physiological function whether involved in the metabolism and detoxification of acrylamide or play a role in protecting the cells from a probable damage. The results of this study, although preliminary, show that proteomics is a valuable tool for toxicity studies, since it allows the analysis of proteins of treated animals in comparison to the control map to establish treatment-related differences.