Abstract: Objective: To investigate the mechanism of defibrase inhibiting the neointimal proliferation after vascular injury. Methods: Oversized tantalum coils were implanted into coronary arteries in 19 dogs. Ten dogs were randomly treated with defibrase （group A） and the others （group B） received two doses of heparin only. The dogs were killed 28 days after the implantation. Histopathology with hematoxylin eosin staining, immunohistochemisty with α Actin monocolon antibody and in situ hybridization were employed to investigate the neointimal and to detect the proliferation of vascular muscle cells and the expression of C-fos oncogene. A computer image analysis system was used to measure the neointimal thickness and the stain density indexes of α Actin and C-fos. Results: The neointimal thickness, the expression of α Actin and the transcription of C-fos oncogene were lower in group A than in group B. Conclusion: Defibrase decreased the intimal hyperplasia, which might be the results of inhibiting the proliferation of vascular muscle cells by decreasing the expression of C-fos oncogene.