Objective: Among various environmental carcinogens, arsenic is highly sensitive and possesses potential to cause several diseases including cancer. Nevertheless, arsenic has not been observed to induce mutation directly but is involved in epigenetic changes. Hypomethylation of oncogenes and hypermethylation of tumor suppressor genes are reported to be associated with accumulation of arsenic. The present investigation demonstrates a direct correlation arsenic and deoxyribonucleic acid (DNA) methylation. Methods:Swiss albino mice were grouped as control and arsenic treated for 12 weeks. Arsenic concentration in blood and testes was analyzed by atomic absorption spectrometer. Furthermore, DNA was extracted from the testes of mice by DNA purification kit and used for determining global methylation in mice genome with the help of MethylFlash Methylated DNA Quantification Kit.Results: Arsenic concentration in arsenic-treated mice was significantly higher than the control group in both blood and testes. Interestingly, arsenic concentration in blood was recorded to be higher than testes in the arsenic-treated group with significance (p<0.0001). Moreover, a lower percentage of cytosine of mice genome was found to be methylated in arsenic-treated mice group than control group (p<0.0001). Conclusion:Greater concentration of arsenic in mice leads to hypomethylation of mice genome globally. Arsenic fosters deregulation of gene expression by modifying methylation of CpG island of the promoter region. Epigenetic study is of prime importance in the field of oncology. Drug development for repressing alteration of DNA methylation is imperative for cancer treatment.