Abstract: Objective: To study the expression of matrix metalloproteinase-9(MMP-9) and vascular endothelial growth factor(VEGF) in retinoblastoma(RB) and its relationship with the differentiation and optic nerve infiltration of RB,and to investigate the role of MMP-9 and VEGF in the infiltration and metastasis of RB and their clinical significance.Methods: Immunohistochemical technique was used to detect the protein expression of MMP-9 and VEGF in 47 cases.Results: The positive rate of MMP-9 protein and VEGF protein expression in 47 cases were 46.8% and 78.7%,respectively.The expression of MMP-9 and VEGF was significantly higher in the undifferentiated pattern than in the rosetted pattern(P<0.05);and the expression of MMP-9 and VEGF was significantly higher in tumors with optic nerve invasion than in those without optic nerve invasion(P<0.005 and P<0.05).In RB,the expression of MMP-9 had a positive correlation with the expression of VEGF.Conclusions: In RB,high expression of MMP-9 and VEGF is related to the invasion and metastasis of RB.The expression of MMP-9 has a positive correlation with the expression of VEGF.The expression of MMP-9 and VEGF may act as a biological marker for the invasion and metastasis of RB,and might be helpful to filter cases of high risk for metastasis and to predict prognosis of the patients.