To investigate the effect of TGF-β2 antisense oligode- oxynucleotide on differentiation, proliferation of subconjunctival fibroblast following glaucoma filtration surgery. · METHODS: Glaucoma filtration surgery was performed on both eyes of 28 rabbits. TGF-β2 antisense oligodeoxynucleotide was subconjunctivally injected in the right eyes (group A),and TGF-β2 missense oligodeoxynucleotide (group B) or PBS (group C) was used at the same method in the left eyes as controls. Rabbits were killed at 4, 7, 14 and 28 days after surgery. Intraocular pressure (IOP), bleb characteristics were recorded at different time point. Subconjunctival fibroblasts were examined by immunohistochemistry and electron microscopy. · RESULTS: The IOP of rabbits in group A was significantly lower at 14 days (6.74±1.18mmHg) and 21 days (8.15±1.97mmHg) after operation than the IOP in group B (8.53±1.04, 9.72±1.09mmHg; P <0.01) and group C (8.79±1.21, 9.43±1.27mmHg; P <0.05). The mean bleb survival time was longer (17.2 days) in group A than that of group B (14.5 days) and group C (13.5 days) (P <0.05). The population of the cells expressing α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) was significantly reduced in group A compared with the group B and C. The ultrastructure of fibroblast was not altered by TGF-β2 antisense oligodeoxynucleotide. · CONCLUSION: TGF-β2 antisense oligodeoxynucleotide can prevent the scar formation after glaucoma surgery by inhibiting the differentiation and proliferation of subconjunctival fibroblast. It could be a potentially useful anti-scarring alternative for the prevention of late surgical failure.