AIM: To investigate the expression of EMMPRIN, MMP1, MMP9 and TIMP2 in retinoblastoma (RB) and normal retinal tissues and their clinicopathological significance and interrelationship. METHODS: Envision immunohistochemistry stainings of EMMPRIN, MMP1, MMP9 and TIMP2 were performed in 30 enucleated eyeballs with retinoblastoma and 15 specimens of normal retina tissue, which had been routinely imbedded with paraffin. RESULTS: Positive rate of EMMPRIN, MMP1, MMP9 expression was higher in RB tissue than in normal control ( P<0.01), while TIMP2 expression was lower in RB than in normal retinal tissue ( P<0.01). Samples from RB cases of clinical stage I, differentiated type, and life span ≥ 2 years had lower positive rate in expression of EMMPRIN, MMP1, MMP9 than those from RB cases of clinical stage III, undifferentiated type, andP life span<2 years ( P<0.05 or <0.01), while samples from RB cases of differentiated type, optic nerve unaffected, and life span ≥ 2 years had markedly higher positive rate in expression of TIMP2 than those from RB cases of undifferentiated type, optic nerve involved and life span<2 years ( P<0.05 or P<0.01). In RB tissues, EMMPRIN, MMP1, MMP9 expressions were highly consistent ( P<0.05), whereas TIMP2 expression is highly inconsistent with EMMPRIN,MMP1,MMP9 expression levels( P<0.05). CONCLUSION: The expression level of EMMPRIN, MMP1, MMP9 and TIMP2 may be an important marker of RB progression, invasion and prognosis. There exist internally mutual regulation relations among them."