OBJECTIVES: The aim of the present study was to analyze the effect of systemic administration of nicotine on bone healing in osseous defects in the tibia of rabbits. MATERIAL AND METHODS: Sixteen female rabbits received nicotine (n=8; test group) or saline (n=8; control group) via subcutaneously placed mini-osmotic pumps for 8 weeks. The animals underwent three surgical operations during the experimental period, and body weight was registered weekly. Blood samples were collected to determine cotinine and prostaglandin E(2) levels. Bone preparations were made in the right leg of all rabbits after 4 weeks and in the left leg after 6 weeks of nicotine/placebo exposure. Thus, 2- and 4-week healing groups were created for the bone defects. After 8 weeks, the animals were killed. Tissue blocks including the bone defects were prepared for histological analysis. RESULTS: The animals in the test group lost weight, while the control group gained weight during the experiment. The prostaglandin E(2) levels in plasma increased significantly following nicotine exposure in the test group. No significant differences in the percentage of vessels and bone density in the osseous defects were found between the test and the control groups after 2 and 4 weeks of healing. CONCLUSIONS: In this experiment, systemic administration of nicotine over 4 or 6 weeks, respectively, influenced body weight and systemic prostaglandin E(2) levels but not the amount of blood vessels and the bone mineral density in bone defects after 2 or 4 weeks of healing.