Arsenic (As) is accumulated in rice grain due to environmental reasons such as polluted ground water and soil, and As toxicity constitutes a serious threat to human health. However, the accurate information required for understanding As-responsive mechanisms remain mostly unknown in rice. Here, we performed the comparative genome-wide transcriptome analysis between As tolerance type (ATT) rice mutant induced by γ-irradiation and its wild type (WT). As compared to WT after As treatment of 150 ppm, ATT exhibited the phenotypic differences such as vigorous growth in shoots and root hairs, and low accumulation of H2O2 in rice roots. In transcriptome analysis, we found between WT and ATT that As toxicity commonly affected to inhibit gene regulations involved in photosynthesis, mitochondrial electron transport and lipid biosynthesis metabolism. While, many genes associated with cysteine synthesis metabolism considerably up regulated in both As-treated plants. Additionally, we found the potential As tolerance-related genes involved in abiotic stress-responsive mechanism and RNA-protein synthesis for protein degradation and modification. To further analyzes the genetic variations of As-responsive genes, the DNA polymorphic DEGs associated with oxidoreductase significantly distributed in ATT more than in WT.