Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory mucosal disease with persistent accumulation of T cells in the lamina propria. Nuclear factor-kappa B (NF-κB) is a major regulator of immune responses, and NF-κB-dependent cytokines and pro-inflammatory mediators can be detected in higher levels in the saliva and serum from patients with OLP. CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells play an important role in the prevention of autoimmune pathology by regulating the immune response. To explore the correlation between NF-κB p65 activation and accumulation of Treg cells in patients with OLP, 40 ethnic Chinese patients with OLP and 10 healthy volunteers were recruited. The nuclear expression of NF-κB p65 in infiltrated mononuclear cells and Treg cells in the OLP lesion and the normal oral mucosa (NOM) was analyzed by immunohistochemistry assay. Our results showed that both the nuclear expression of NF-κB p65 and the number of Foxp3(+) Treg were higher in the OLP lesions. Furthermore, the frequency of Treg cells was negatively correlated with NF-κB nuclear expression in subepithelial lymphocytic infiltrate of the OLP lesion. This finding provides a new insight into the pathogenesis of OLP and may contribute to novel therapeutic strategies for the treatment of OLP by modulating the immune system.