The study was to compare the preventive effects of the local application of mitomycin C (MMC) and 10-hydroxycamptothecin (HCPT) on reducing intraarticular adhesion after knee surgery in rabbit model. Thirty-six New-Zealand rabbits were randomly and equally divided into three groups: MMC, HCPT and control group. Approximately 10 mm×10 mm of the cortical bone was removed from both sides of left femoral condyle and the cancellous bone underneath was exposed. The exposed decorticated areas were covered with cotton pads soaked with MMC (0.1 mg/ml), HCPT (0.1 mg/ml) and physiological saline for 10 min. The left knee joint was then fixed in the fully flexed position with a Kirschner wire for 4 weeks after surgery. The rabbits were killed after 4 weeks and multiple parameters including the macroscopic evaluation, the hydroxyproline content, the histological evaluation and the fibroblast counts were used to evaluate the effect of MMC and HCPT on preventing intraarticular adhesion. The results showed that weak fibrous adhesions were found around the decorticated areas in MMC group and moderate intraarticular adhesions were found in HCPT group. However, there were severe fibrous adhesions around the decorticated areas in control group. The hydroxyproline contents and the fibroblast numbers of MMC and HCPT group were significantly less than those of control group. In conclusion, our data showed that topical application of MMC and HCPT could prevent intraarticular adhesion after knee surgery in rabbit model, but MMC had a better preventive effect than that of HCPT.