Orthodontic treatment induces various biological responses, including tooth movement and remodeling of alveolar bone. Although some studies have investigated the contribution of orthodontic procedures to changes in saliva conditions, little is known about the effects of different treatment durations on the saliva proteome. To identify the discriminating protein profiles in unstimulated whole saliva of orthodontic patients with different treatment durations, we used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with magnetic bead, and peptide mass fingerprints were created by scanning MS signals. Saliva samples from 40 patients (10 in each of four groups: the group without an appliance and groups under treatment for 2, 7, and 12 months) were analyzed. The results showed eight mass peaks with significant differences. Furthermore, mass peak intensities at proteins 1817.7, 2010.7, 2744 and 2710.2 Da represented a steady time-dependent increasing trend, whereas protein 4134 Da exhibited a decreasing tendency. Differential expression of the peptidome profile also occurred in the multiple comparisons, and we established a fitting model. Thus, the potential discriminating biomarkers investigated in this study reflected the complicated changes in periodontal tissues during orthodontic treatment and indicated dynamic interactions between orthodontic treatment and the saliva proteome. The results provide novel insights into alterations in salivary proteins due to different orthodontic treatment durations and may lead to the development of a therapeutic monitoring strategy for orthodontics. (C) 2012 Elsevier Inc. All rights reserved.