Arsenic is a common environmental and occupational contaminant worldwide which can influence the development of respiratory diseases. In recent years, alteration in the lifestyle as well as food habits have led to increased consumption of food containing high levels of fat. The present study was designed to evaluate the effects of chronic exposure to a high-fat diet (HFD) on arsenic-induced damages and oxidative stress in the lung tissue of mice. This is the first study to reveal the effect of diet-induced obesity on arsenic-induced lung damages. Seventy-two male Naval Medical Research Institute (NMRI) mice were divided into six groups and fed an HFD or standard diet (SD) while being exposed to 25 or 50 ppm of arsenic through drinking water for 20 weeks. At the end of the experiment, the lung weight to body weight ratio; oxidative stress markers, nitrite level, and hydroxyproline content in the lung tissue; and lung histology were evaluated. The results demonstrated that arsenic exposure leads to a significant decrease in the glutathione level and catalase enzyme activity, and significantly increased reactive oxygen species, malondialdehyde, and nitrite level, but it did not affect the superoxide dismutase activity and hydroxyproline content in the lung tissue. Consequently, all the parameters studied aggravated when HFD was consumed along with arsenic. These findings were confirmed by histological examination. Our study showed that HFD increased arsenic-induced lung damages through oxidative stress in mice. These findings could be important for clinical research to protect against arsenic-induced respiratory toxicity in humans.