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ABSTRACTThe study aimed to investigate the effect of fermented n-hexane extract of Pentaclethra macrophyllaseeds (FPMSE) in an experimental model of glaucoma. Eighteen rabbits (1-1.8 kg body weight) were allocated into six groups of three rabbits (six eyes per group). Group 1 was the normal control. Ocular hypertension was induced with 1% prednisolone acetate ophthalmic solution in groups 2-6, twice daily for 21 days. Group 2 received no treatment, while groups 3–6 received 5 mg/kg b.w. acetazolamide, 100, 200, and 300 mg/kg b.w. extract, respectively. The intraocular pressures and other biochemical parameters were evaluated. The existence of bioactive compounds was determined via phytochemical analysis. Compared to group 2, the administration of FPMSE resulted in a significant decrease in IOP in the treated groups. Malondialdehyde concentrations in the treated groups’ aqueous humor and plasma were considerably lower (p < 0.05) than in group 2. Compared to group 2, glutathione, nitric oxide, and antioxidant levels improved significantly (p < 0.05). C-reactive protein and glutamate levels in group 2 were comparable (p > 0.05). FPMSE substantially reduced phospholipase A2activity. Histological assessment of the ciliary body showed adequate pigmentations in the treatment groups compared to group 2. Hence, FPMSE possesses ocular hypotensive effects.