In this study, our objective was to evaluate effects of leptin on fracture healing in rats. Seventy two male Sprague-Dawley (SD) rats were randomized into 3 groups. Standardized femoral fractures were created in all the rats. Group A was treated with 1 mL normal saline (NS), group B with 0.3 μg/kg leptin in 1 mL NS, and group C with 0.5 μg/kg leptin in 1 mL NS for 2 weeks intraperitoneally. Each group was divided into three subgroups including 8 rats for evaluation at 2, 4 and 8 weeks. Radiological evaluation showed that callus formation of group B and C was all significantly higher than group A at 8 weeks (P=0.04 and P=0.013, respectively). There was no statistically significant difference in fracture healing between group B and group C at 8 weeks (P=0.197). Histological evaluation revealed fracture healing of group B and C was better than group A at 4 weeks (P=0.01 and P=0.002, respectively) and 8 weeks (P=0.008 and P=0.003, respectively). Micro-computed tomography (Micro-CT) analysis demonstrated that greater amounts of bony callus and evidence of bone fusion were observed in group B and C at 4 weeks (P=0.02 and P=0.04, respectively) and 8 weeks (P=0.005 and P=0.001, respectively) compared to group A. Group C also had better fracture healing than group B at 8 weeks (P=0.01). In conclusion, leptin has a positive effect on rat femoral fracture healing.