There is a large amount of information available regarding the chemical structure and biological activity of superoxide dismutase (SOD), which is abundantly generated by Mycobacterium tuberculosis in the early stages of growth. SOD is a strong superoxide radical scavenger, which plays a significant role in resisting oxidative stress. On the other hand, SOD mutant strains have been constructed to define the role of this molecule in the immune response to M. tuberculosis infection. These studies have suggested that the absence or attenuation of SOD can motivate innate immunity and SOD avoid destruction or growth inhibition of M. tuberculosis. For detailed investigation of how SOD proteins aid M. tuberculosis survival within macrophages, we cloned 2 SOD genes (SODA and SODC) from the M. tuberculosis H37Rv genome, overexpressed, identified, and purified the proteins, and then exposed macrophages to the proteins. Following this, we assessed NO production, the secretion of cytokine interferon-γ (IFN-γ) and intercellular adhesion molecule-1, the expression of IFN-γ receptor and Toll-like receptor 2 on the surface of macrophages, and caspase-3 enzyme activity as well as macrophage apoptosis. Our results showed that both SODA and SODC proteins considerably reduced the production of NO and oxygen radicals and impaired cell immunologic function in early infection.