Purpose: To assess the quantitative differences in the levels of members of the transforming growth factor (TGF-β), matrix metalloproteinase (MMP), and tissue inhibitor of MMP (TIMP) families in the aqueous humor (AH) between patients with acute primary angle closure (APAC) and those with cataract only. Methods: AH samples were collected from 26 patients with APAC and cataract as well as 26 patients with age-related cataract only. Multiplex assays were used to measure the concentrations of TGF-β1, TGF-β2, and TGF-β3; MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10; and TIMP-1 and TIMP-2. Results: The concentrations of TGF-β1, TGF-β2, MMP-2, ( p < 0.001), and TIMP-1 were significantly higher (all p < 0.001) in AH samples from patients with APAC versus cataract only. Conversely, the AH concentrations of MMP-7 ( p = 0.524), MMP-9 ( p = 0.103), MMP-10 ( p = 0.111), and TIMP-2 ( p = 0.059) did not significantly differ between the groups. The concentrations of TGF-β3 and MMP-1 were below the respective detection limits in most AH samples. Conclusion: The AH levels of TGF-β1, TGF-β2, MMP-2, and TIMP-1 were elevated in APAC eyes. Such altered protein levels could induce abnormal deposition of extracellular matrix in the trabecular meshwork, resulting in an increase in aqueous outflow resistance and, thereby, providing a possible explanation of the mechanism of residual glaucoma after cataract surgery.