Randomized, double-blinded, animal model. The objective of this study is to evaluate the effect of pentoxifylline (PTX) on spinal fusion in a rabbit model. Previous studies assert that PTX increases new bone formation. Because PTX seems to have these profound effects on bone metabolism, it may be hypothesized that it may enhance spinal fusion. Twenty-four New Zealand white rabbits were randomized and each received single-level posterolateral, inter-transverse process fusion with autologous iliac crest. In group 1, 12 male New Zealand white rabbits were treated with intravenous PTX treatment in 100-mg/kg/day dose after the surgical procedure. In group 2, 12 received no PTX medication and were accepted as the control group. Nine weeks after surgery, the animals were killed. The spines were tested via a manual palpation test, biomechanical testing, plain radiography, computed tomographic scans, and histomorphometric analysis. The fusion rates of manual palpation were 40% in the control group and 80% in the PTX group (P = 0.17). Using a 5-grade radiographical system, the mean fusion grade was 2.4 in the control group and 3.1 in PTX group (P = 0.012). Total displacement of the fused level for the control group under flexion and extension was 0.2515 mm and was lower for the PTX-treated group: 0.1266 mm (P = 0.012). In the control group, the mean bone volume of the fusion mass determined from computed tomographic analysis was 4.0678 cm, whereas in the PTX group it was 4.7802 cm (P = 0.009). The mean trabecular bone area was 14% and 19% for the control and PTX groups, respectively (P = 0.002). The differences between groups was statistically significant in terms of radiological fusion grading, biomechanical testing, volume of the fusion mass, and percentage of trabecular bone area. These results suggest that PTX may have a beneficial effect on spinal fusion. 2.