The purpose of this study was to determine whether high levels of plasma nicotine, delivered via subcutaneously placed mini-osmotic pumps, had an effect on bone development and osseointegration of a titanium implant in rat femurs in both the short and long term. In this study, we hypothesized that systemic nicotine may not affect bone development, but may affect osseointegration in both the short and long term. Thirty rats were assigned to 4 groups. Group 1 (n = 10) was subdivided into 2 groups, which both received nicotine during the duration of the experiment. Half of the group (n = 5) was sacrificed at 2 weeks after implant placement, and the other half (n = 5) was sacrificed at 4 weeks after implant placement. Group 2 (n = 10) was treated identically; however, this group was given saline placebo rather than nicotine. Nicotine/saline was administered via subcutaneous mini-osmotic pumps. Serum analysis was assessed biweekly and weight was assessed weekly. Implant placement consisted of mini-implant placement in the femur of the rats under general anesthesia. After sacrifice, the femurs were harvested and analyzed. Biomechanical push-in test was used to determine the degree of osseointegration by evaluating the breakpoint load. Micro-CT was performed on the femurs of the remaining 10 rats to determine the bone density and architecture. Micro-CT showed no significant difference in bone morphometric analysis. Push-in test showed significant difference in axial load force required to dislodge the implant between the nicotine-treated and control rats both at 2 and at 4 weeks after implant placement. The evidence indicates that while there was no significant difference in bone development and remodeling with exposure to systemic nicotine, there was a significant difference in bone wound healing, specifically with the osseointegration of titanium implants at both 2 and 4 weeks after implant placement. In conclusion, systemic nicotine may have a significant impact on the osseointegration of implants in the rat femur. Additional studies need to be conducted to further understand the specific way in which nicotine adversely affects wound healing on the molecular level.