Object. The authors conducted a study to determine the effectiveness of mitomycin C (MMC) in preventing epidural fibrosis in rats which underwent craniectomy. Methods. Craniectomies were performed in the right frontoparietal region; after the procedure the animals had been divided in 2 groups of 10 each. Cotton pads soaked with 0.1mg/ml MMC or saline (control) were applied to the operative sites. Four weeks after craniectomy the rats were sacrificed, and epidural fibrosis was evaluated histologically. The dura mater thickness, the density of epidural fibrosis, arachnoidal involvement, and bone regeneration were determined. Results. No obvious adhesion formed in the rats in the MMC group, but severe epidural adhesions were found in control group. The duramater thickness, the density of epidural fibrosis, and arachnoidal involved rat number in the MMC group were significantly lower than in control groups. Conclusions. Epidural fibrosis can be a devastating condition that forms after craniectomy. Topical application of mitomycin C may be a successful method of preventing epidural fibrosis following craniectomy.