Hypoxia induces reactive oxygen species (ROS) production in periodontal tissues. Superoxide dismutase 3 (SOD3) is an enzyme protecting�cells from ROS. This study investigated SOD3 expression and function during rat orthodontic tooth movement�(OTM) and in hypoxia-exposed rat PDL�cells. OTM of right maxillary first molars were performed in Sprague-Dawley rats for 1 and 14 days (n�= 6 per group). SOD3 and HIF-1? expression were evaluated by immunohistochemistry. SOD3 effects on cell viability and proliferation, ROS production, and mRNA expression of�Hif-1?,�Rankl,�and�Opg�in PDL cells and osteoclast differentiation were investigated under normoxia�and hypoxia. SOD3 expression in PDL tissues decreased on compression side on day 1 and on both sides on day 14. HIF-1? levels significantly increased on compression side on day 14. Cell viability, cell proliferation, and�Opg�mRNA expression decreased, whereas ROS production and�Hif-1?�and�Rankl�mRNA expression increased in SOD3-silenced PDL cells. Hypoxia reduced�Sod3�and�Opg�mRNA expression and increased ROS,�Rankl�mRNA expression, and osteoclast formation; SOD3 treatment attenuated these effects. Therefore, SOD3 plays a role in periodontal remodelling during OTM and in hypoxia-exposed PDL cells through ROS, HIF-1?, and RANKL/OPG pathways.