Background: Macrophages play a pivotal role in the development of emphysema and depending on the microenvironment stimuli can be polarized into M1- or M2-like macrophage phenotypes. Aim: To compare macrophage polarizations in cigarette smoke (CS)- and porcine pancreatic elastase (PPE)-induced emphysema models. C57BL/6 mice were subdivided into four experimental groups. In the PPE group, animals received an intranasal instillation of PPE (0.677 IU); in the Saline group, animals received an intranasal instillation of Saline (0.9%). Animals from both groups were euthanized on the 28th day. In the CS group, animals were exposed to CS for 30 minutes, twice a day, 5 days per week for 12 weeks. In the Control group, animals received filtered air. Results: We observed an increase in total macrophages for both experimental models. For M1-like macrophage markers, we observed an increase in TNF-α+ and IFN-γ+ cells, Cxcl-9 and Cxcl-10 expressions in PPE and CS groups. Only for CS group, we detected an increased expression of IL-12b. For M2-like macrophages markers, we observed a down regulation for IL-10, IL-4, IL-13, Arg1 and Fizz1 and an increase of TGF-β+ cells for PPE group while for CS group there was an increase in TGF-β+ cells and IL-10 expression. All exposure groups were compared to their respective controls. Conclusions: In summary, we demonstrated that CS- and PPE-induced models resulted in different microenvironmental stimuli. CS exposure induced an environmental stimulus related to M1- and M2-like macrophage phenotypes similar to previous results described in COPD patients, whereas the elastase-induced model provided an environmental stimulus related only to the M1 phenotype.