Abstract: Objective: The purpose of this study was to observe the immunohistochemical localization of RANKL(receptor activator for nuclear factor-κB ligand) and OPG(osteoprotegerin) and bone resorption in induced periapical lesions in rats.Methods: 8 -week-old male Wistar rats were use in this study, and those whose one side of their mandibular first molar pulp cavity was exposed to the oral cavity served as the treated group and those of the other side as control. Animals were randomly sacrificed at 1st day, 3rd day, 7th day, 14th day and 21st day after operation. We removed the jaw of rats, took X- ray to observe the apical lesion and sections were prepared for immunohistochemistry to detect RANKL / OPG expression in various stages of periapical tissue. Results: Rats periapical bone lesion area significantly increased from the 3rd day, reaching the peak at 21st day, which was time-dependent. RANKL expression of 3rd day group dramatically increased, reached the peak at 7th day, and began to decrease at 14th day. OPG expression sharply increased at 1st day and smoothly rose after 3rd days until it reached the peak at 21st days. The study found a significant correlation between the expression of RANKL/OPG system and the development of periapical lesions. Conclusions: RANKL / OPG system plays an important regulatory role in periapical inflammatory bone destruction.