Our aim was to evaluate the effect of an intraoperative single dose of retinoic acid (RA) or mitomycin C (MMC) in preventing posterior capsule opacification (PCO). Twenty-seven rabbits were divided randomly into three groups. RA (250 microg/ml) and MMC (0.04 mg/ml) were given 0.1 ml by hydrosection and 0.9 ml into the capsular bag after phacoemulsification. The third group served as a control group. Three months after intervention PCO was graded clinically. Furthermore, proliferation of lens epithelial cells was evaluated histologically. Two eyes developed corneal edema in the MMC group. On clinical assessment, RA and MMC were significantly effective in preventing PCO compared with controls (P<0.005). On histological analysis, there was significantly reduced proliferative activity on posterior capsules in the treatment groups, in contrast to multilayer cells in the control group. Intraoperative single-dose administration of RA and MMC significantly prevented the development of PCO in rabbit eyes. The optimal biocompatible dosage must be carefully determined by further investigation.