Increasing evidence indicates that bone remodeling is under the control of factors related to neuronal regulation, but the underlying mechanisms remain largely unknown. The aim of this study is attempted to assess the effect of denervation on neuropeptide expression and bone remodeling-related factors in the periodontal tissue regeneration process. rats underwent transection of the left inferior alveolar nerve (IAN-T) and surgery to produce bilateral periodontal defects; then, alveolar tissue was obtained from the animals of each group at 1, 2, 4, 6 and 8 weeks after the operation. The expression levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) were quantified by real-time PCR and Western blot techniques, and immunohistochemical staining was applied to investigate the in situ expression of OPG and RANKL. Osteoclasts were identified by tartrate-resistant acid phosphatase staining. The expression levels of calcitonin gene-related peptide (CGRP) mRNA and substance P (SP) mRNA were also quantified by real-time PCR. Mandibles with only periodontal defects were used as controls. After denervation, the OPG/RANKL ratio was reduced in the IAN-T groups due to decreased OPG mRNA and protein (P < 0.05) and a simultaneous increase in RANKL mRNA and protein expression (P < 0.05). On the other hand, the number of osteoclasts in periodontal defect areas increased, especially at 2 weeks, and at this time point, the expression of RANKL mRNA and protein peaked. The mRNA expression levels of neuropeptides CGRP and SP mRNA were monitored throughout the entire progress and exhibited a trend that was similar to that of the OPG/RANKL ratio, i.e., a downward trend over 1-2 weeks, an increase until 6 weeks, then back to the normal levels at 8 weeks. Innervation influences the OPG/RANKL ratio and neuropeptide expression, both of which govern the periodontal alveolar bone regeneration processes.