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Background: RNA N6-methyladenosine is a key step of post-transcriptional modulation which involves in governing gene expression. The m6A modification catalyzed by Mettl3 has been widely recognized as a critical epigenetic regulation process for tumorigenic properties in various cancer cell lines, including bladder cancer. However, the in vivo function of Mettl3 in bladder cancer remains largely unknown. Methods: Establishment of transgenic mouse model for exploring the role and mechanisms of Mettl3 in bladder cancer. Coupled global transcriptome sequencing and methylated RNA immunoprecipitation sequencing is performed to identify targets modulated by Mettl3.Results: We found that ablation of Mettl3 in bladder urothelial attenuates the oncogenesis and tumor angiogenesis of bladder cancer. In addition, conditional knockout of Mettl3 in K14+ bladder cancer stem cell population leads to inhibition of bladder cancer progression. And deletion of Mettl3 leads to the suppression of TEK and VEGF-A through reduced abundance of m6A peaks on specific region. Conclusions: Taken together, Mettl3-mediated m6A modification is required for the activation of TEK-VEGF-A-mediated tumor progression and angiogenesis. Our findings may provide theoretical basis for bladder cancer treatment targeting Mettl3.