Aim: To study and compare the effect of both hyaluronidase and plasmin in induction of posterior vitreous detachment (PVD) and vitreous liquefaction in rabbits. Subjets and Methods : The study was performed on 40 white New Zealand rabbits .Twenty rabbits had one eye injected with hyaluronidase (20 IU/ 0.1 ml ) .The other 20 rabbits had one eye injected with plasmin (1 IU /0.1 ml). The fellow eye of all rabbits was injected with lactated Ringer's solution as a control. The specimens were examined after 2 and 4 weeks of injection using light microscopy and scanning electron microscopy.Results: The control eye of all rabbits revealed no histopathological changes. Group A (2 weeks after hyaluronidase injection) revealed no histopathological changes resembling the control group. Group B (4 weeks after hyaluronidase injection) revealed partial PVD in 70% of cases and no effect on the rest of cases with disorganization of photoreceptors in 30% of cases. Group C (2 weeks after plasmin injection) revealed partial PVD in 80% of cases and no effect in the rest of cases with no disorganization of photoreceptors. Group D (4 weeks after plasmin injection) revealed total PVD in 80% of cases and partial PVD in the rest 20% of cases with no photoreceptors disorganization. No retinal hemorrhage or oedema were detected in any group. Conclusion: The safety of intravitreal hyaluronidase and plasmin in induction of PVD has given encouraging results .The duration factor plays an important role in their effect with more effect in having longer duration of action. Plasmin, however, is more effective than hyaluronidase in PVD induction inspite of having lower concentration in the same duration of action.