Background: Despite some advances in the discovery of novel therapies, smoke inhalation injury remains a difficult to treat critical health issue due to its physiopathological complexity. Natural products, such as D-limonene (LIM), are becoming an important potential source of new treatments in many health problems. LIM has been shown to have antioxidant, anti-inflammatory and protective effects in respect of several diseases, including respiratory conditions. Objective: The aim of this study was to evaluate the effects of inhaled LIM on acute smoke-induced lung injury in rats. Methods: Thirty minutes after smoke inhalation, adult male Wistar rats were treated with vehicle or LIM (0.01 mg/kg) for 30 min. Blood samples, and the liver, lungs, and trachea were collected for analysis. Results: The results showed that LIM minimized the injuries, reducing oxidative and inflammatory damage by improving catalase (CAT) (p < 0.05), and superoxide dismutase (SOD) activities (trachea: p < 0.01; lung: p < 0.05) and reducing interleukin-1 beta (IL-1β) level (p < 0.01) caused by smoke inhalation. LIM was also able to ameliorate damage in both trachea and lung tissues. Conclusions: The results indicate that LIM has a beneficial effect on lung injury, mainly by reducing oxidative stress, anti-inflammatory response and tissue damage.