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To evaluate the efficacy of α-lipoic acid (ALA) in reducing scarring after trabeculectomy.Eighteen adult New Zealand white rabbits underwent trabeculectomy. During trabeculectomy, thin sponges were placed between the sclera and Tenon’s capsule for 3 minutes, saline solution, mitomycin-C (MMC) and ALA was applied to the control group (CG) (n=6 eyes), MMC group (MMCG) (n=6 eyes), and ALA group (ALAG) (n=6 eyes), respectively. After surgery, topical saline and ALA was applied for 28 days to the control and ALAGs, respectively. Filtrating bleb patency was evaluated by using 0.1% trepan blue. Hematoxylin and eosin and Masson trichrome staining for toxicity, total cellularity, and collagen organization; α-smooth muscle actin immunohistochemistry staining performed for myofibroblast phenotype identification.Clinical evaluation showed that all 6 blebs (100%) of the CG had failed, whereas there were only 2 failures (33%) in the ALAG and no failures in the MMCG on day 28. Histologic evaluation showed significantly lower inflammatory cell infiltration in the ALAGs and CGs than the MMCG. Toxicity change was more significant in the MMCG than the control and ALAGs. Collagen was better organized in the ALAG than control and MMCGs. In immunohistochemistry evaluation, ALA significantly reduced the population of cells expressing α-smooth muscle action.ΑLA prevents and/or reduces fibrosis by inhibition of inflammation pathways, revascularization, and accumulation of extracellular matrix. It can be used as an agent for delaying tissue regeneration and for providing a more functional-permanent fistula.