To investigate intraocular tolerance to heavy silicone oil (Densiron-68) as a long-term vitreous substitute in the experimental animal and to provide reference for further clinical test and application. METHODS: Twenty-one New Zealand albino rabbits, weighing 2.2 to 2.5kg, underwent pars plana vitrectomy of the left eye. Animals were randomized in 3 groups: group 1: Densiron-68 group, 9 rabbits; group 2: silicone oil group, 9 rabbits; group 3: 3 rabbits eyes were injected balanced salt solution(BSS) as a control group. During the follow-up period, the eyes were examined by slit-lamp biomicroscopy and indirect ophthalmoscopy, and the intraocular pressure was measured by Schiotz tonometer. The eyes were then enucleated at the 4^th,-8^th and 12^nd week after surgery respectively and processed for light microscope and transmission electron microscope. RESULTS: Throughout the observation period in all groups there was unremarkable findings of the retina,optic nerve,and no corneal edema, intraocular hemorrhage, endophthalmitis were noticed. No statistic difference of intraocular pressure was noticed between control group and two experiment groups or within each group preoperatively or postoperatively. A large clear bubble was formed after Densiron-68,-silicone oil were injected into vitreous cavity. Densiron-68 depicted dispersion beginning between 3^rd and 8^th week. Only one posterior subcapsular lens opacity was observed in Densiron-68 tamponade group. Histological evaluation of the retina exposed to Densiron-68 or silicone oil showed normal retinal structures by light microscopic examination. The mitochondria swollen in the inferior photoreceptor inner segment were observed after 4 weeks in Densiron-68 injection group. The changes mentioned above were more remarkable after 8 weeks. But only a few mitochondria in the photoreceptor inner segment were swollen slightly after 12 weeks. The similar changes were in inner nuclear layer(INL) cell in the superior retina after 12 weeks in silicone oil tamponade group. CONCLUSION: Densiron-68 can be well tolerated by retinas of rabbit, although its propensity to disperse, the availability of Densiron-68 may add to our repertoire in managing selected RD. The mitochondria swollen in the inferior photoreceptor inner segment are observed in Densiron-68 injection groupe. It needs more study to evaluate the damage to anterior chamber and cornea. Densiron-68 should not be used to silicone oil-dependent patient because its propensity to disperse and should be extracted as soon as possible after retina reposition.