The aim of this study was to histologically evaluate and compare the effects of the systemic administration of l-thyroxine (TX) and doxycycline (DX) on orthodontically induced root resorption, Twenty-eight male 50- to 60-day-old Wistar rats were used. Seven rats served as the baseline control. Seven animals received TX (20 mu g/kg bodyweight/day) and seven DX (1.2 mg/kg bodyweight/day), by means of a mini-osmotic pump implanted subcutaneously. Seven rats were separated as a sham, in order to evaluate the pure effect of the surgical procedure on the animals' health. Tooth movement (TM) was achieved with a continuous force of 50 g by placing Elgiloy coil springs between the right maxillary first molar and incisors for 14 days. The animals were sacrificed and specimens containing the appliance and maxillary tooth-bearing segments were processed for light microscopy. The surface area of root resorption lacunae was measured histomorphometrically using digital photomicrographs. To evaluate the resorptive changes on the molar root surface of each group, scanning electron microscopy (SEM) examinations were also carried out. Statistical evaluation of root resorption percentages was performed using Kruskal-Wallis analysis of variance test. Multiple comparisons were determined by the Student-Newman- Keuls method. The level of significance was set at P < 0.05.