Objectives: Activation of Nuclear Factor Kappa B (NFKB) in response to stimulation of Receptor Activator of NF Kappa B (RANK) by Receptor Activator of NF Kappa B-Ligand (RANK-L) is vital for bone remodeling. Activation involves proteosomal degradation of I Kappa B (IKB) allowing NFKB to enter the nucleus. Recently, phosphorylation of NFKB p65 has been shown to reduce the ability of IKB to interact with NFKB and thus present a means to by pass or augment traditional NFKB activation. We tested whether phosphorylation of p65 occurs during orthodontic tooth movement (OTM). Methods: An orthodontic force of 40 grams was applied to maxillary molars of male rats that were then sacrificed at various times thereafter. Tooth movement was measured and teeth and underlying alveolar bone was fixed, demineralized, embedded in paraffin, sectioned and stained with an antibody that detects phosphorylated NFKB p65. Additional staining was performed on mouse marrow cultures stimulated to produce osteoblasts and osteoclasts. Results: Little phosphorylation of p65 was detected in control rats in which no orthodontic force was applied. Increased phosphorylation of p65 was detected and was associated with cells of the periodontal ligament at 24 hours and 7 days after force application. Staining was detected in osteoclasts and other cells in both areas of tension and compression. Phosphorylation was also detected in mouse marrow osteoclasts cultured in vitro. Conclusions: Our data suggest that NFKB p65 is phosphorylated during OTM in bone cells including osteoclasts. This phosphorylation may serve to augment NFKB activation triggered by factors like RANK-L and TNFa. Supported by NIH grants DE13857 (CD) and AR47959 (LSH)