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Many patients regularly take histamine receptor antagonists, such as cetirizine, to prevent allergic reactions, but these antiallergic drugs may have inadvertent effects on orthodontic treatment. In previous studies, histamine has been shown to modulate the sterile inflammatory reaction underlying orthodontic tooth movement. Pertinent effects of histamine antagonization via cetirizine during orthodontic treatment, however, have not been adequately investigated. We thus treated male Fischer344 rats either with tap water (control group) or cetirizine by daily oral gavage corresponding to the clinically used human dosage adjusted to the rat metabolism (0.87 mg/kg) or to a previously published high dosage of cetirizine (3 mg/kg). Experimental anterior movement of the first upper left molar was induced by insertion of a nickel-titanium (NiTi) coil spring (0.25 N) between the molar and the upper incisors. Cone-beam computed tomography (CBCT), micro-computed tomography (µCT) images, as well as histological hematoxylin-eosin (HE), and tartrate-resistant acid phosphatase (TRAP) stainings were used to assess the extent of tooth movement, cranial growth, periodontal bone loss, root resorptions, and osteoclast activity in the periodontal ligament. Both investigated cetirizine dosages had no impact on the weight gain of the animals and, thus, animal welfare. Neither the extent of tooth movement, nor cranial growth, nor root resorption, nor periodontal bone loss were significantly influenced by the cetirizine dosages investigated. We, thus, conclude that histamine receptor antagonist cetirizine can be used during orthodontic treatment to prevent allergic reactions without clinically relevant side effects on orthodontic tooth movement.