The multifunctional cytokine interleukin-6 (IL-6) has actions on multiple cell types, including promotion of the development of immune cells and osteoclasts. Periapical inflammation as the result of root canal infection is characterized by the accumulation of inflammatory cells and bone resorption. The effect of IL-6 on periapical lesion formation after pulpal infection is unknown. We sought to determine whether deletion of IL-6 affects periapical lesion formation after pulp exposure.