Although the amount of chemicals in heated tobacco products (HTPs) aerosols is reduced compared to conventional combustible cigarette smoke, the association between HTPs and reduced health effects remains unclear. In this study, we hypothesized that exposure to IQOS, an HTP, would increase oxidative stress and affect the secretion of inflammatory cytokines. First, C57BL/6 mice exposed to IQOS aerosols were evaluated to determine the adverse effects of IQOS exposure. IQOS exposure significantly decreased the concentration of GSH in alveolar macrophages in a dose-dependent manner and increased the percentage of GSSG in lung tissues. These results indicate that IQOS exposure increases oxidative stress, and GSH is consumed to remove oxidative stress. In addition, foamy alveolar macrophages were observed in the bronchial alveolar lavage fluid after IQOS exposure. Although the concentration of inflammatory cytokines, IL-6, and GM-CSF, in the plasma increased significantly after IQOS exposure, there were no significant changes in other cytokines. These results indicate that short-term exposure to IQOS aerosols may increase oxidative stress and induce the secretion of inflammatory cytokines. Lastly, the longer-term effects of IQOS aerosols exposure should be evaluated in the future.