Two-dimensional electrophoresis followed by MALDI TOF MS analysis (2-DE MALDI-TOF-MS) and multi-dimensional liquid chromatography followed by ESI-IT MS/MS analysis (MuD LC ESI-IT-MS/MS) have been two major approaches for proteome analysis. Although both approaches are known to have advantage and disadvantage over the each other, many of comparative studies have not been performed.In the present study, we conducted a direct comparison between 2-DE MALDI and MuD LC-ESI-IT on plasma proteome analysis. A combination of Cibacron Blue and ProteinG columns was used for the removal of albumin and IgG from plasma, and the sample was further fractionated with ion exchange column. This prefractionation method enables us to explore lower abundant proteins in plasma. A schematic draw of this approach is shown in the figure. Currently we carry out protein identification by both methods. A comparative list of those proteins identified by 2-DE MALDI and MuD LC ESI-IT will be presented.Moreover, evaluation of an albumin and IgG removal method using anti human albumin and IgG antibodies will be also reported.