Aim: We aimed to determine the effects of rt-PA and enoxaparin on post laminectomy epidural fibrosis and to compare the effects of these two medications with hyaluronic acid and urokinase in an experimental model of spinal epidural fibrosis. Method: Forty Spraque-Dawley rats were anaesthetized by intraperitoneal anesthesia (ketamin 8 mg/100 g) and randomly allocated to five groups. All groups were underwent L1-2 total laminectomies. Topical medications were applied to group 2-5 right after the laminectomy space. Hence, in group 1 (G1=control) only laminectomy was constituted, in group 2 (G2) laminectomy + topical Urokinase, in group 3 (G3) laminectomy + topical rt-PA, in group 4 (G4) laminectomy + topical enoxaparin and in group 5 laminectomy + topical Hyaluronic acid (G5) application were performed. The potentials of local urokinase, rt-PA, hyaluronic acid and enoxaparin in preventing the production of epidural fibrosis were assessed. Result: In inter group comparison, G1-G2, G1-G3, G1-G4, G1-G5 groups differed from each other for total scar score, middle scar score and deep scar score (p<0.05). However, G2-G3, G2-G4, G2-G5, G3-G4, G3-G5 and G4-G5 were not different from each other. Conclusion: In rats, the topical thrombolysis with fibrinolitic agents is safe and efficacious in preventing of post laminectomy epidural fibrosis. Thrombolytic therapy with topical hyaluronic acid, rt-PA, urokinase and enoxaparin may come to play an important role in the prevention of post operative spinal epidural fibrosis and arachnoiditis. Based on the results we found that rt-PA and enoxaparine inhibit the formation of epidural scar adhesions and arachnoiditis compared with control group.