Abstract： Objective To evaluate the anti-angiogenic effect of eukaryotic vector containing human VEGF 165 and truncated pseudomonas exotoxin A (PE38) fusion gene on malignant glioma in nude mice, and explore a novel anti-angiogenic therapy for cancer. Methods The models were established through hypodermic injection of human U251 glioma cells into the nude mice and randomly divided into untreated group, PBS group, pIRES2-EGFP group and pIRES2-VEGF165-PE38-EGFP group on the 9th day. H&E staining was performed to observe the morphological changes of the glioma tissues; SP immunohistochemistry was employed to detect the expression of GFAP, CD31 andPE; quantitative pathologic image analysis system was used to investigate the microvessel density (MVD) in the tumor tissues. Results At day 16, the pIRES2-VEGF165PE38-EGFP group showed significantly lower tumor volume of mice and significantly decreased MVD than the other three groups (P<0.05). Positive expression of PE was shown in the pIRES2-VEGF165PE38-EGFP group, but negative in the other three groups. Conclusion The expression products of VEGFJ65-PE38 fusion gene can obviously inhibit the growth and angiogenesis of U2S1 cells in nude mouse flank tumor models, suggesting that it may be a novel therapeutic approach for anti-angiogenic therapy of cancer.