Background/Aim: A positive association of body mass index (BMI) with inorganic arsenic (iAs) metabolism parameters (percentage dimethylarsinic acid [%DMA] and second methylation index [SMI]) was reported in epidemiological studies, suggesting that obesity improves iAs detoxification. However, BMI is a rough indicator of obesity, which is the product of the balance between calorie intake and physical activity. Physical activity consumes methyl groups that are necessary to metabolize iAs. Therefore, our objective was to evaluate whether physical activity modifies the relationship between BMI and iAs metabolism.Methods: We performed a cross-sectional secondary analysis of 800 healthy women, 20 years and over, that participated as population controls in a previous study on breast cancer in northern Mexico. Participants were interviewed about physical activity during their lifetime, and their weight and size were obtained. Concentrations of urinary arsenic metabolites were determined by high performance liquid chromatography coupled with mass spectrometry.Results: In the study population, total arsenic ranged from 0.71 to 303.29 µg/L, BMI from 14.60 to 57.81 kg/m2, and the lifetime average physical activity from 0 to 13.14 h/week. BMI was significantly and positively associated with %DMA and SMI. These associations remained after stratifying for physical activity. A significant antagonistic interaction (p=0.003) emerged only between physical activity and SMI on BMI: BMI association with SMI differed between women with higher (β= 0.004 95% CI: 0.001, 0.007) and lower physical activity (β= 0.011, 95% CI: 0.007, 0.015).Conclusion: Our findings do not support a direct relationship between BMI and iAs metabolism. Physical activity appears to play an important role in iAs detoxification in obese women. This finding warrant further research.