Significant advancements in imaging and surgical methodologies have led to more frequent performance of neurosurgical procedures such as laminectomy in both animal and human patients. Epidural fibrosis (EF) is defined as the excessive formation of scar tissue in the epidural space after lumbar laminectomy, often resulting in recurring postoperative pain. Given the association between postoperative hematoma accumulation at the laminectomy site and the development of EF, the present study aimed to evaluate the preventive impact of tranexamic acid (TXA), an antifibrinolytic agent with well-recognized hemostatic properties across various surgical fields. A rabbit laminectomy model was constructed to assess its effectiveness in reducing EF formation. A total number of 18 adult New Zealand White male rabbits were randomly divided into two groups: The control (saline) group and the treatment (topical TXA) group. Each rabbit underwent a two-level laminectomy at L3-L4. The treatment group received 5.00 mL of 100 mg mL TXA solution applied topically to the laminectomy site, while the control group received 5.00 mL of saline. Postoperative evaluations included magnetic resonance imaging at week six to assess EF, followed by histopathological examinations to evaluate fibroblast cell density in scar tissue, EF grading and thickness of the dura mater. The analysis of magnetic resonance imaging and histopathologic data revealed significant differences between the two groups indicating that topical administration of TXA might be a promising approach for preventing EF.