It has been proposed that disruption of normal vitreous humor may permit O 2 to travel more easily from the retina to the center of the lens where it may cause nuclear cataract (Barbazetto et al., 2004;Harocopos et al., 2004). In the present study, we injected enzymes intravitreally into guinea pigs (which possess an avascular retina) and rats (which possess a vascular retina) to produce either vitreous humor liquefaction plus a posterior vitreous detachment (PVD) (with use of microplasmin) or vitreous humor liquefaction only (with use of hyaluronidase), and 1-2 weeks later measured lens nuclear pO 2 levels in vivo using a platinum-based fluorophore O 2 sensor (Oxford-Optronix, Ltd.). Experiments were also conducted in which the animals were allowed to breathe 100% O 2 following intravitreal injection with either microplasmin or hyaluronidase in order to investigate possible effects on O 2 exchange within the eye. Injection of guinea pigs with either of the two enzymes produced no significant differences in lens pO 2 levels 1-2 weeks later, compared to controls. However, for the rat, injection of microplasmin produced a 68% increase in O 2 level in the center of the lens, compared to the controls (5.6 mmHg increasing to 9.4 mmHg, p<0.05), with no corresponding effect observed following similar use of hyaluronidase. Treatment of guinea pigs with microplasmin dramatically accelerated movement of O 2 across the vitreal space when the animals were later allowed to breathe 100% O 2 (for example, O 2 traveled to a location directly behind the lens 5 times faster than control; p<0.01); however, the effect following treatment with hyaluronidase was significantly less. When microplasmin-injected rats breathed 100% O 2 , the time required for O 2 to reach the center of the lens was 3 times faster than control (0.4 min compared to 1.4 min, p<0.01). The results have implication with regard to the occurrence of age-related PVD in the human, and a possible acceleration of maturity-onset nuclear cataract. In addition, enzymatic creation of a PVD to increase the rate of O 2 exchange within the vitreal space may have potential application for treatment of retinal ischemic disease.