We investigated the effect of colchicine in a sustained drug delivery system on posterior capsule opacification (PCO) in rabbit eyes. A polymer matrix wafer, which diffused colchicine at a steady rate, was implanted in the capsular bag of 34 eyes after the lens material was removed by endocapsular phacoemulsification. Three different drug concentrations were used in the rabbit eyes, which were compared with control eyes containing the polymer matrix wafer without colchicine. The mean PCO score was highest in the control group without colchicine and increased steadily over 12 weeks. The rate of PCO formation in all eyes treated with colchicine was significantly lower than in the control group. There was no statistically significant improvement in PCO inhibition with the higher colchicine dosages. Side effects included inflammatory anterior chamber reaction and corneal and retinal complications and were most notable with the highest drug concentration. Slow release of colchicine reduces PCO formation in the rabbit. The optimal biocompatible dosage must be carefully determined and warrants further investigation.