Aim To investigate the change of cyclooxygenase-2 in hypercholesterolemic rabbits carotid artery injured by balloon and the relationship with intimal hyperplasia. Methods Twenty-five New Zealand male rabbits were studied. They were fed with atherogenic diet. Four weeks later, balloon injury was conducted in right carotid artery respectively. A few rabbits were killed at 6 h, 24 h, 1 W, 2 W and 4 W. Blood samples and right carotid artery were collected in time. Intimal hyperplasia was studied by histological morphology method. The expression of tissue cyclooxygenase-2 mRNA was determined by reverse transcription-polymerase chain reaction. Result Intimal hyperplasia was present at day 7 after balboon injury, became more obvious at day 14 and in progression at day 28. The media area was not changed. The intima/media ratio increased as time went on (0.032±0.004,0.030±0.003, 0.030±0.002, 0.251±0.045, 1.111±0.182 and 1.448±0.216). No change was observed in control group. Cyclooxygenase-2 mRNA expression was trace in the carotid atery of the hypercholesterolemic rabbits without balloon injury (0.5±0.21, 0.5±0.25, 0.6±0.19, 0.6±0.26 and 0.5±0.22). The expression increased significantly after balloon injury as time went on (0.6±0.22, 0.8±0.24, 1.2±0.31, 1.6±0.36 and 1.4±0.32). After balloon injury cyclooxygenase-2 expressed stronger in injury group than in control group. Conclusions Cyclooxygenase-2 expressed stronger in injury group than in control group, which indicated that cyclooxygenase-2 may play an important role in restenosis caused by balloon injury.