The current study sought to examine the interactions between inflammatory and immune events in the lung and circulating interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) levels at different burn depths with concomitant smoke inhalation in the rat model. Forty-eight female Sprague-Dawley rats were divided into six groups: S, sham; P, partial-thickness burns; F, full-thickness burns; I, inhalation; Pi, partial-thickness burns + inhalation; and Fi, full-thickness burns + inhalation. Blood samples and lung biopsies were obtained 24 hours later. Blood levels of IL-6, TNF-α, and IF-γ were measured with enzyme-linked immunosorbent assay. The proportions of CD3+ lymphocytes and CD68+ macrophages in the biopsies were studied immunohistochemically. The most severe inflammatory changes, except the neutrophil sequestration, were observed in the Fi group. A dense amount of neutrophils was observed in the F group. Edema and massive alveolar bleeding were seen in the I, Pi, and Fi groups. The amount of CD3+ lymphocytes were dense in the P, F, and Pi groups. The amount of CD68+ macrophages were significantly dense in Pi, F, I, and Fi groups. IL-6, TNF-α, and IF-γ increased in all groups when compared to the S group. The highest IL-6 level was seen in the Fi group. TNF-α significantly increased in the F, Pi, I, and Fi groups. Increase in IFN-γ levels in the Pi and Fi groups was significantly higher than in the P and F groups. In concomitant smoke inhalation and skin burns, pulmonary damage and systemic inflammatory response are related and may be evaluated by blood levels of IL-6, TNF-α, and IFN-γ cytokines.