AIM: To investigate expression of factors related to angiogenesis: HIF-1α, iNOS, COX-2 and VEGF in choroidal melanoma and its clinical significance. METHODS: Fifty samples of choroidal melanoma and 15 samples of melanocytic nevi of the eyelid identified by pathology were collected. Immunohistochemistry SP method was used to examine the expression of HIF-1α, iNOS, COX-2 and VEGF in these samples. The comparison among groups was done by SPSS 13.0 software. RESULTS: The positive expression rates of HIF-1α, iNOS, COX-2 and VEGF in choroidal melanoma group were significantly higher than those in eyelid nevi group (χ2=6.5542, 7.7224, 8.5828, 15.1749). The positive expression rate of VEGF was associated with the tumor size (χ2=10.9194), but was not associated with pathological type (χ2=2.0712) and the situation of scleral invasion (χ2=5.4289). The positive expression rate of HIF-1α was associated with the tumor size (χ2=7.1216) and pathological type (χ2=9.0889), but was not associated with the situation of scleral invasion (χ2=3.3586). The positive expression rate of iNOS was associated with the tumor size (χ2=9.5503), but was not associated with pathological type (χ2=1.9450) and the situation of scleral invasion (χ2=2.3810). The positive expression rate of COX-2 was associated with the tumor size (χ2=7.2970), but was not associated with pathological type (χ2=1.8421) and the situation of scleral invasion (χ2=0.4018). The expression of HIF-1α, iNOS and COX-2 were significantly associated with the expression of VEGF (r=0.9429, 1, 0.9857). The expression of COX-2 was significantly associated with the expression of iNOS (r=0.9857). The expression of HIF-1α was significantly associated with the expression of COX-2 (r=0.9857). The expression of HIF-1α was significantly associated with the expression of iNOS (r=0. 9429). CONCLUSION: The expression of HIF-1α, iNOS and COX-2 protein in choroidal melanoma were higher and may relate to angiogenesis and stimulate tumor growth. Determination of HIF-1α, iNOS and COX-2 may be helpful for the diagnosis and therapy of this tumor.