Statement of the Problem: Quercetin is a pharmacological flavonoid that can inhibit high mobility group box1 (HMGB1) protein, a non-histone nuclear protein that is implicated in inflammation. Th17 cells are important cells in the pathogenesis of inflammation. Pulpitis is the inflammation of dental pulp, which usually is accompanied by pain. Quercetin may alleviate this inflammation.Purpose: The current study aimed to compare blocking of HMGB1 function and stimulation of HMGB1 function with quercetin and investigate the effects of the blockage on T helper 17 (Th17) cells and mitogen-activated protein kinase Toll-like receptor 4 (MAPK-TLR4) signaling pathway. Materials and Method: T cells isolated from the pulp involved with pulpitis and the normal pulp were cultured. The cells suspensions were plated in 6-wells culture plates and stimulated with 0.5 µg/ml of HMGB1 for 2, 4, 8, and 12 hours. For blocking TLR4, 10 µg/ml rabbit anti-human TLR4 antibody was added 1 hour before treatment with HMGB1. Results: The level of these cytokines decreased; moreover, western blot data showed that quercetin could decrease MAPK signaling pathway by means of inhibition of HMGB1 on T cells. The results showed the reduction of TLR4 pathway and Th17 cell polarization.Conclusion: Our results indicated that the levels of IL-17, IL-33, and IL-6 in supernatants from patients’ cultured T cells were increased after stimulation with HMGB-1 following employing quercetin. It also could inhibit MAPK signaling pathway, which subsequently could decrease Th17 production and IL-17. Quercetin could decrease pro-inflammatory cytokines and IL-17 production.