Introduction: The purpose of this study was aimed t Introduction: o evaluate the effects of administering two immunosuppressive drugs, mycophenolate mofetil and sirolimus on orthodontic tooth movement in dogs. Methods: Fifteen adult healthy dogs were equally di Methods: vided into three groups, group1, the control did not receive any drugs while dogs in groups 2 and 3 received mycophenolate mofetil and sirolimus, respectively. A 100 gm force was applied to the left and right sides of the maxillae in all groups using nickel titanium coil spring attached to the lateral incisors and canines for 42 days. Tooth movement was assessed by measuring differences in the distance between the lateral incisors and canines on days 0 and 42. At day 42, the dogs were euthanized and the maxillae were dissected, teeth and the surrounding alveolar bone were processed for histological examination. Results: Histological results showed newly formed b Results: one at the tension side of the control group while the pattern of bone resorption seen at the pressure side indicated the presence of front and direct bone resorption. Less bone deposition and resorption were observed at the tension and compression sides in mycophenolate mofetil treated dogs while in the tension side of sirolimus treated dogs, little or no bone apposition was present and similarly, little or no bone desorption was observed at compression sides. Moreover, there was a statistically significant difference between the tooth movement among the three groups at day 42 (p<0.001). Within each group, there was a significant difference between tooth movement at days 0 and 42 in groups 1 and 2 (p=0.05) but group 3 showed no significant difference (p>0.05) Conclusions: Both mycophenolate mofetil and SLR sig Conclusions: nificantly altered orthodontic tooth movement; however mycophenolate mofetil seems to be less disruptive than sirolimus to the pattern of orthodontic tooth movement.