Macrophages are the first immune cells to interact with inhaled bacilli, and they have the ability to suppress bacterial growth through phagocytosis. Two distinct phenotypes can be found within granuloma. First, mycobacteria are eliminated more quickly and are killed by proinflammatory (M1). Second, anti-inflammatory macrophages (M2), are intended to preserve tissue integrity and support tissue repair. Therefore, the current study used histopathological examination to classify tuberculous granuloma into four stages (stage I to stage IV) and immunohistochemistry (IHC) to investigate the expression of MAC387, CD163, and Arginase 1 in naturally infected Beef cattle with tuberculosis at different Stages of TB granulomas. Immunohistochemical analysis revealed that the immunolabeling of MAC387+ macrophages significantly reduced as the stage of granuloma increased from stage I to stage IV (P <0.008). However, the immunolabeling of Arg1+ and CD163+ macrophages significantly increased as the stage of granuloma increased from stage I to stage IV (P<0.01, and P<0.001, respectively).