Purpose: Uremia influences bone remodeling. This study aimed to evaluate the impact of treatment with local injection of Vitamin D3 (Vit.D3) on bone remodeling associated with orthodontic treatment in uremic rabbits. Patients and Methods: rabbits were split into four groups: a healthy control, a sham second group, where antibiotic was given in therapeutic dose, uremic third group, uremia induced by a nephrotoxic dose of antibiotic, and the fourth uremic group treated with locally injected Vit.D3. All groups experienced orthodontic procedures. Bone density before and after tooth movement was determined using quantitative computed tomography. Analysis of serum parathyroid hormone was done by Elisa while serum calcium, urea, and creatinine were done by enzymatic colorimetric assay. Maxillary bone underwent histological analyses. Results: A statistically significant reduction in bone density in uremic models (P< 0.05) versus healthy models. Improvement in bone density in the treated uremic group after treatment with locally injected Vit.D3, which led to increase osteoblastic activity in comparison to the non-treated uremic group. A significant negative correlation was detected between serum calcium and bone density in the non-treated uremic group, this correlation was lost in the treated uremic group. Conclusions: Treatment of uremic models with locally injected Vit.D3, had significantly improved bone density by increasing osteoblastic and decreasing osteoclastic activity regardless of calcium and parathyroid levels. Local Vit.D3 could be used to improve bone remodeling in uremia.