Primary open angle glaucoma (POAG) is defined as an optic neuropathy characterized by loss of optic nerve axons and retinal ganglion cells. Increase of intraocular pressure (IOP) is a major risk factor for POAG, which is partially due to an abnormally high aqueous humor outflow resistance in trabecular meshwork (TM). Trabecular outflow pathway is a key element in drainage of aqueous humor. Malfunction of TM in POAG is associated with over expression of inflammatory markers, cellular senescence, oxidative stress, and decrease of cellularity. The biological changes of TM cell and extracellular matrix compromise trabecular pathway drainage resulting in an increased IOP. This article reviewed the progression in research on aqueous humor outflow pathway emphasizing the alteration of trabecular pathway.