Introduction: Osteocalcin is a bone protein that has been used to mark bone turnover. The precise role of this protein in bone remodeling has not been fully elucidated; however, it was shown to be instrumental in the activation of osteoclastic bone resorption via its effect on osteoblasts. Fluoride influences bone growth by acting as a mitogenic agent for osteoblasts. In this study, we used a rodent model to determine the effects of fluoride administration on systemic osteocalcin during orthodontic tooth movement. Methods: Thirty-two 8-week-old female Wistar rats were divided into 4 groups. The first experimental group (n = 10) was fed a normal laboratory diet and distilled water (MilliQ). The second experimental group (n = 10) had the same diet with the addition of fluoridated water. All animals in both groups had 100-g nickel-titanium coil springs secured to their mandibular incisors and left first molars to instigate orthodontic tooth movement for 14 days. The third (n = 6) and fourth (n = 6) groups were the controls. These animals did not undergo orthodontic tooth movement and were given fluoridated (100 ppm sodium fluoride) and nonfluoridated water ad libitum. Phlebotomy was performed via the lateral tail vein before placement of the orthodontic appliances, and final blood samples were obtained via cardiac puncture after the rats were killed 2 weeks later. Serum was isolated from the samples after centrifuging at each stage of phlebotomy, and an enzyme-linked immunosorbent assay (ELISA) was subsequently performed to determine osteocalcin levels in the various sample groups. Results: Orthodontic tooth movement with high, continuous forces was found to have a positive, statistically significant correlation with serum osteocalcin expression in the rodent model. The use of fluoride as a variable was found to increase the mean osteocalcin concentration, but this was not statistically significant. Conclusions: Further understanding of the biological implications of increased osteocalcin expression requires additional research into the local expression of this protein in the gingival crevice during orthodontic movement.