No single biologic marker is used in the routine diagnosis of acute cerebral infarction. We screened for potential biomarkers in 92 plasma samples, including samples from 32 patients with acute cerebral infarction and 60 hospital control subjects. Pretreated plasma samples were analyzed using SELDI-TOF-MS (Ciphergen Biosystems, Fremont, CA). Proteomic spectra of mass to charge ratio (m/z) were generated by the application of plasma to weak cation exchange (CM10 ProteinChip, Ciphergen Biosystems) arrays. A differential pattern consisting of 13 biomarkers was selected based on their collective contribution to the optimal separation between patients with acute cerebral infarction and control subjects with a sensitivity of 84.4% and specificity of 95.0%, respectively. Plasma proteomic profiling with SELDI-TOF-MS and ProteinChip technologies shows potential in discriminating patients with acute cerebral infarction and control subjects. Diagnosis of acute cerebral infarction should probably depend on the use of a panel of biomarkers.