AIM: To evaluate the short-term efficacy and safety of ultrasound cycloplasty (UCP) procedure in Chinese patients with angle-closure glaucoma (ACG), and the mechanisms of its intraocular pressure (IOP) lowering effects. METHODS: Fifty-six patients (56 eyes) diagnosed with primary and/or secondary ACG were enrolled in this prospective study. Visual acuity, IOP, slit-lamp examinations, structural parameters of anterior segments including anterior chamber depth (ACD), pupillary diameter (PD), anterior chamber area (ACAr), anterior chamber angle (ACAn), and side effects were evaluated. Seven rhesus macaques (Macaca Mulatta) were used for the analyses of IOP lowering effects, including inflammatory reactions, pathohistological evaluation, scanning electron microscopy (SEM), and aqueous outflow pathway via 1% basic fuchsin perfusion. RESULTS: Fifty six eyes of 24 male and 32 female patients with an average age of 58.93±15.97 years old were recruited in primary and secondary ACG affected 31 and 25 eyes, respectively. Clinically, the mean IOP was 17.89±7.93 mm Hg (n=53, 53.63% reduction, P<0.001) at 1wk and 22.47±12.00 mm Hg at 12mo (n=16, 18.67% reduction, P<0.01) after UCP, compared to the baseline of 39.08±14.75 mm Hg (n=56). Postoperative tolerance was favorable in 94.64% of cases, with visual acuity unchanged or improved in 96.43% of patients. Mild and transient inflammatory reactions were observed post UCP. UBM analysis revealed statistically significant changes in anterior chamber parameters: increased ACD (n=22, P<0.05), enlarged PD (n=22, P<0.05), expanded ACAr (n=16, P<0.01), and widened ACAn (n=19, P<0.05) compared to preoperative measurements. As in normal monkey eyes, IOP was also reduced upon UCP. Mild inflammatory reactions were seen 1-7d post treatment. Hematoxylin and Eosin (H&E) staining showed enlarged spaces among ciliary muscle bundles. Ciliary process stromal edema was evident, but significant loss of two layers of ciliary epitheliums was not seen. SEM confirmed ciliary muscle fibers concentrated. Fuchsin anterior chamber perfusion showed the whole ciliary body staining in UCP group, but only surface staining in controls. CONCLUSION: UCP is efficient and safe to lower the IOP of patients with ACG. Changed anterior chamber structure and increased aqueous humour outflow via uveoscleral pathway may significantly attribute to IOP lowering effects of UCP.