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Objective: A new genre of smoking, heat not burn cigarette (IQOS), has been developed for tobacco products that are increasingly used among the public. With this method, nicotine is evaporated by heating the tobacco at lower temperatures without burning. Firms producing IQOS method claim that the smoker is protected from oxidant molecules formed as a result of combustion. Although there are few in vitro studies on this subject, sufficient in vivo experimental studies have not been performed yet. In literature %70 of tobacco studies are conducted by cigarette firms and we aimed to compare the probable effects of IQOS and combustible cigarette use on rat models as an independent researchers. Method: This study was designed as a randomized prospective rat trial. We used 21 Wistar albino male rats divided into 3 groups. The control group exposed to air only, while one group exposed to whole-body combustible cigarette mainstream smoke (10 mg nicotine/day) and the other group exposed to IQOS aerosol (combustible cigarettes equivalent nicotine-10 mg/day) for 3 weeks, 1.5 hours a day, 7 days a week with the smoke inhalation machine designed with the Department of Physics Engineering of İstanbul Technical University. Once a week, the levels of nicotine, inflammation parameters interleukin (IL) (IL-1ß, IL-6, tumor necrosis factor (TNF)-α), oxidative stress parameters (total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) and mononuclear leukocyte DNA damage analyzed in the blood. In addition, the lung tissues of the sacrificed rats’ removed, and the levels of oxidative stress and inflammation parameters examined. Results: The variations between the groups’ TAS, TOS, OSI, IL-6, IL-1ß, and TNF-α levels were examined through the posthoc tests and the Dunn test. The difference among the inflammatory marker levels of the combustible cigarette group and the control group was found statistically significant (p<0.001); however, IQOS group’s values were insignificant with regard to others’. TOS, OSI, IL-6, IL-1ß levels of the combustible cigarette group is statistically higher, yet; TAS level is lower compared to the control group. Conclusion: Increased oxidative stress in the combustible cigarette group may be associated with the short duration of the study. Therefore it is needed to support the stated data with long term in vivo researches. [ABSTRACT FROM AUTHOR]