To identify proteins differentially expressed in schizophrenia patients, we collected 50 microl cerebrospinal fluid from 17 first-episode schizophrenia patients and 10 healthy controls.Their proteins were separated by two-dimensional gel electrophoresis without using any depletion method and identified by mass spectrometry.Approximately 550 spots were detected, six of which had significantly different intensities in schizophrenia compared to control specimens. We were able to validate in individual samples the upregulation of apolipoprotein E, apolipoprotein A1 and prostaglandin-H2 D-isomerase by Western blot analyses and detect the downregulation of transthyretin, TGF-beta receptor type-1 and coiled-coil domain-containing protein 3 precursor.These findings may help to elucidate the disease mechanisms and confirm the hypothesis of disturbed cholesterol and phospholipid metabolism in schizophrenia, and thus reveal the final role players. Moreover, a grouped protein expression analysis of apolipoprotein E, apolipoprotein A-I, and prostaglandin-H2 D-isomerase in cerebrospinal fluid from patients might be a potential diagnostic tool for schizophrenia.