Background/Aim: Epidural fibrosis is one of the problems that can be seen after spinal surgery. The aim of this study was to investigate the possible preventive role of medical ozone (O) treatment on epidural fibrosis. Materials and Methods: Twenty-four Sprague Dawley rats were randomly split into four groups: control (C), O, laminectomy (L), and L+O groups. Animals in the C group were sacrificed at the beginning of the experiment. The L and L+O groups had L procedure, while O treatment was supplied for the O and O+L groups. After 42 days of follow-up, for histological evaluation and biochemical measurements, the ratio of epidural fibrosis and catalase (CAT) with malondialdehyde (MDA) levels in serum, respectively, were analyzed in terms of statistical differences. Results: Histologically, a distinct difference was o bserved in the epidural space after O treatment. A significant difference in epidural fibrosis areas is found to be between the O, L, and O+L groups (P < 0,0001). There was no statistically significant difference between CAT and MDA levels that were obtained by spectrophotometric analysis. Conclusion: Histological results suggest that medical O treatment after L can be used as an alternative method to prevent epidural fibrosis. Further studies with wide cohorts and interval measures are required to detail the effects of doses.