Acetylcholine is an endogenous alpha4beta2 and alpha7 nicotinic receptor agonist that is basally secreted in the lungs of mammals. Agonism of these receptors has been associated with an increased Th2 immune response, decreased Th1 and Th17 immune responses. Using high performance liquid chromatography, lungs of BALB/c mice infected with Mycobacterium tuberculosis (Mtb.) H37Rv, revealed an increased level of acetylcholine expression in lung two weeks and two months after infection. These elevations may be associated with immunopathological progression of the disease (inefficient granuloma formation, increased lung pneumonia and bacillary burdens). Mice therefore received saline solution (control group), and either receptor selective antagonist: alpha4beta2 nicotinic or alpha7 nicotinic during both periods of acetylcholine exacerbation. Mice lungs were obtained after treatment of each group and Mtb colony-forming units (CFUs) and morphometric analysis were realized. Administration of nicotinic receptor antagonists resulted in larger granulomas and lower pneumonic areas and CFUs when compared with the control group. The cholinergic system may hence emerge as a novel therapeutic target in treating TB infection, improving the host's response during the disease.