Purpose: A biochemical approach to implant surface modification may offer an alternative to physicochemical and morphologic methods for obtaining desirable bone-implant interfaces. The objective of this study was to investigate the bone tissue response to anodized titanium implant surfaces coated with a poly(D,L-lactide-co-glycolide) (PLGA) solution mixed with 1α,25-diydroxyvitamin D3 (1α,25-(OH)2D3) via an electrospray technique. Materials and Methods: Threaded implants were manufactured and anodized under 300 V at 660 Hz for 3 minutes (control group). Half of the implants were then coated with 0.15 mL of the PLGA/1α,25-(OH)2D3 solution (5 µg/implant) via electrospray (experimental group). Surface topography was evaluated using field-emission scanning electron microscopy and optical interferometry. Forty-eight implants (12 implants per group per healing period) were surgically placed in random sites in the tibiae of 12 New Zealand white rabbits. After 4 and 12 weeks of healing, undecalcified ground sections were subjected to histologic and histomorphometric analyses. Results: At week 4, the mean bone-to-implant contact ratio (BIC%) over the entire length of the implant in the experimental group was 37.08% ± 10.18%, versus 28.01% ± 8.70% in the control group. The mean BIC% value in the first four consecutive threads of the experimental group was 48.64% ± 15.92%, compared to 36.11% ±13.49% in the control group (P .05). At week 12, the mean overall BIC% values were 39.10% ± 7.68% in the experimental group and 29.53% ± 9.49% in the control group. The mean BIC% value in the first four consecutive threads of the experimental group was 51.80% ± 16.41%, versus 37.35% ± 11.77% in the control group (P .05). Conclusion: The current study demonstrated that the PLGA/1α,25-(OH)2D3 solution coating resulted in submicron-sized particles, which may stimulate bone formation adjacent to the surface of implants inserted into bone. Keywords: 1α, 25-dihydroxyvitamin D3, anodized titanium implant, histomorphometry, poly(D, L-lactide-co-glycolide)