Tumor microenvironment, in particular tumor angiogenesis, forms a niche that facilitates rapid tumor growth and metastasis. We have reported ERG, an ETS family transcription factor downregulated within the tumor endothelial cells (ECs), is critical for increasing H3K27ac enrichment and mRNA transcription on EC-specific genes (Nuc Acids Res 2016, PLoS Genet 2018). However, the role of ERG in tumor angiogenesis is unclear. Here we successfully generated EC-specific mouse ERG-transgenic mouse (Erg^iEC/Cdh5-Cre-ERT2;Erg) and evaluated the tumor growth and angiogenesis in Lewis Lung Carcinoma (LLC)-transplantation model. We observed differential angiogenesis patterns: a decrease in blood vessel number, a 1.5-fold increase in pericytes coverage, and a 7 % expansion of blood vessel diameter within the tumor in Erg^iEC mice. And Erg^iEC mice showed a 15 % decrease in tumor size in basal conditions, meanwhile, a significant 50 % decrease with a combination of anti-cancer drug cisplatin-treated conditions. RNA-sequencing analysis additionally revealed differential gene expression patterns related to inflammation, cell cycle, and cell growth on the smaller tumor tissues in the cisplatin-treated Erg^iEC mice than in the cisplatin-treated control mice. These results suggested that the transcriptional regulation of ERG was crucial for modulating EC function and the normalization of tumor blood vessel environment via preventing ERG transcriptional decrease was a novel molecular target for developing cancer drugs.