AbstractApical periodontitis is a disease caused by bacterial invasions through the root canals. Our previous study reported that lithium chloride (LiCl) had a healing effect on apical periodontitis. The aim of this report is to investigate the healing properties and mechanism of lithium ion (Li+) for apical periodontitis using rat root canal treatment model. 10-week-old male Wistar rat’s mandibular first molars with experimentally induced apical periodontitis underwent root canal treatment and were applied lithium carbonate (Li2CO3) containing intracanal medicament. Base material of the medicament was used as a control. Subject teeth were scanned by micro-CT every week and the periapical lesion volume was evaluated. The lesion volume of Li2CO3 group was significantly smaller than that of the control group. Histological analysis showed that in Li2CO3 group, M2 macrophages and regulatory T cells were induced in the periapical lesion. In situ hybridization experiments revealed a greater expression of Col1a1 in Li2CO3 group compared with the control group. At 24 h after application of intracanal medicament, Axin2-positive cells were distributed in Li2CO3 group. In conclusion, Li2CO3 stimulates Wnt/β-catenin signaling pathway and accelerate the healing process of apical periodontitis, modulating the immune system and the bone metabolism.