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This study aimed to examine the expression of signaling transduction proteins and their possible correlation with different clinical subtypes of oral lichen planus (OLP).We examined the immunoexpression and phosphorylation status of 21 signaling transduction proteins of OLP (n = 10) and normal groups (n = 8) using PathScan analysis. Using immunohistochemistry, we detected expression of STAT-3 and p38 MAPK in tissues of OLP (n = 40) and normal controls (n = 10).PathScan analysis showed that STAT-3 (Ser727) expression in normal control (N), reticular OLP (R-OLP) and erosive OLP (E-OLP) group was gradually elevated (R-OLP vs N, P = .001; E-OLP vs N, P < .001; E-OLP vs R-OLP, P = .002). Immunohistochemistry showed that STAT-3 expression in the epithelium of normal control, reticular OLP and erosive OLP was consistent with PathScan analysis (R-OLP vs N, P < .001; E-OLP vs N, P < .001; E-OLP vs R-OLP, P = .036). Both PathScan (P = .012) and immunohistochemistry (P < .001) showed that, p38 MAPK expression was significantly higher in OLP compared with normal controls. However, a significant difference was not seen between the reticular OLP and erosive OLP groups.Our results indicate that STAT-3 may be involved in OLP development and progression and account for different clinical manifestations.