Objective: One of the important causes of failed back surgery is the extensive peridural fibrosis collecting in the surgical field after spinal surgeries. Today we know that inflammatory mechanisms mediated by the immune system of the body plays an important role in generation of fibrosis. Azithromycin, a macrolide antibiotic, has proven immunomodulatory effects in various diseases. This study aims to investigate the effects of azithromycin on peridural fibrosis Methods: Twenty-four Wistar rats received laminectomies before dividing them into three groups randomly. Animals of the control group received normal saline intraperitoneally while animals in the treatment groups received low (20 mg/kg) and high (80 mg/kg) doses of azithromycin intraperitoneally after surgical interventions. The amount of fibrosis, fibroblast density and inflammatory cell density were analyzed histologically. Results: Analysis demonstrated significantly reduced fibrosis, fibroblast density and inflammatory cell density in treatment groups compared to the control group. There was no difference between the treatment groups. Conclusion: Immune system plays critical roles in tissue repair and fibrogenesis. Results of our study demonstrated that azithromycin application reduced formation of peridural fibrosis in experimental laminectomy model in rats. Further studies with different dose regimes and different application routes are required to carry these results to an advanced level. © W. S. Maney & Son Ltd 2011.