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The potential association between coal-burning arsenic exposure and type 2 diabetes (T2D) was examined through a case control study, conducted in coal-burning arsenic poisoning areas in the Guizhou Province. This study included patients diagnosed with type 2 diabetes. Control subjects without type 2 diabetes were recruited randomly after gender and age 1:1 matching. All subjects completed questionnaire surveys and underwent physical examination and whole blood arsenic level testing. The whole blood arsenic level was associated with a significant increase in the risk of type 2 diabetes (75th versus 25th, adjusted OR = 1.76, 95% CI: 1.03–3.01). However, a nonlinear relationship was observed between the blood arsenic level and type 2 diabetes. The risk of type 2 diabetes increased with blood arsenic levels above 3.69 μg/L (Log As ≥0.57). The subgroup analysis revealed that blood arsenic levels were associated with significantly increased risk of type 2 diabetes in people who ever smoked (P <.05), particularly those who smoked ≥15 years (adjusted OR = 3.15, 95% CI: 1.9–7.28). Therefore, prolonged arsenic exposure, even at a low level, is associated with a higher prevalence of type 2 diabetes in a nonlinear pattern. Blood arsenic levels less than 3.69 μg/L may be considered safe with respect to the risk of T2D. However, smoking, particularly smoking ≥15 years, may be associated with the development of diabetes in patients with arsenic exposure. • Coal-burning arsenic exposure is associated with T2D. • Prolonged arsenic exposure, is associated with T2D in a nonlinear pattern. • Smoking may be associated with T2D onset in patients with arsenic exposure. [ABSTRACT FROM AUTHOR]