Introduction: Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent cancer-causing agent in cigarettes and is also associated with the induction of lung tumors by the stimulation of malondialdehyde (MDA) levels and expression of tumor-associated macrophages (TAMs). The present study aimed to examine the variations of MDA levels and TAM expression in the lung tissues of rats exposed to NNK following 12 weeks of Nigella sativa nanocapsule injection. Methods: In this study, 48 Wistar rats were randomly divided into five groups of supplement, supplement with NNK, NNK, control, and saline. For 12 weeks, NNK was injected subcutaneously per kilogram of the animals' body weight with the weekly dose of 12.5 milligrams. In addition, the nanocapsules were subcutaneously injected once a week per kilogram of the body weight with the weekly dose of 12.5 milligrams. The MDA levels and CD68-TAM expression in lungs were determined using the enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Results: The injection of Nigella sativa nanocapsules for 12 weeks significantly decreased the MDA levels and CD68-TAM expression in the NNK group (P<0.001). Additionally, the injection of Nigella sativa nanocapsules along with the consumption of NNK significantly decreased the MDA levels and CD68-TAM expression in the lung tissues of the NNK group (P<0.001).