To investigate the clearance of vascular endothelial growth factor (VEGF) after the induction of posterior vitreous detachment by plasmin and/or SF(6). The study design included four groups of rabbits: group 1 received an intravitreal injection of plasmin and SF(6) in the right eye, group 2 received an intravitreal injection of plasmin in the right eye, group 3 received an intravitreal injection of SF(6) in the right eye, and group 4 received an intravitreal injection of balanced salt solution in the right eye. Intravitreal injection of human VEGF (50 μL, 10 ng/μL) was performed in study eyes and control eyes 1 month after plasmin and/or SF(6) injection. Serum and vitreous samples were collected on days 1, 3, and 7 after VEGF injection to determine the serum and vitreous concentrations of VEGF. One day after VEGF injection, residual human VEGF concentration in the vitreous cavity was significantly lower in the plasmin- and SF(6)-treated eyes (group 1) and the plasmin-treated eyes (group 2) when compared with the control eyes (group 4) (P = 0.047 and 0.027, respectively). Three days after VEGF injection, the residual VEGF concentration in the vitreous cavity was still significantly lower in the plasmin- and SF(6)-treated eyes (group 1) when compared with the control eyes (group 4) (P = 0.025). Eyes treated with plasmin exhibit a more rapid clearance of exogenous VEGF than control eyes. This finding suggests a novel treatment for retinopathies associated with vitreous traction and VEGF elevation.