Objective: is to evaluate the effect of systemic administration of Omega-3 fatty acids on orthodontic tooth movement (OTM) with histological analysis. Materials and Methods: OTM was induced in 20 adult albino New Zealand rabbits with NiTi coil spring for 21 days. Omega-3 or Saline was given every day via oral gavage during experimental period. Animals were sacrificed for histomorphometric analysis of alveolar bone remodeling after 21 days of OTM. Results: A significant difference in OTM amount was found in the 3rd week of OTM with means (1.445 ± 0.13), (1.72 ± 0.15) for experimental and control groups, respectively. Histomorphometric analysis showed a significant reduction in the area of active bone-resorptive lacunae and a significant decrease in osteoclastic activity related to omega-3 group after 3 weeks. A significant difference in osteoclast count is found, omega-3 group about (0.21 ± 0.09) while control group about (0.33 ± 0.11). Conclusions: A strong evidence of the osteoclastic inhibitory effect of systemic Omega-3 had been found which decreased percentage and amount of OTM.