ABSTRACT Objective To investigate the histological influence of waterpipe smoke exposure on lung tissues of Swiss mice during the periods of 7, 15, 30, 60, and 90 days. Methods The sample consisted of 60 animals, divided into 6 groups, one control group, exposed only to air, and the other experimental groups, daily submitted to water pipe smoke for 30 minutes through the whole body system, for 7, 15, 30, 60 and 90 days. After these periods, the mice were euthanized to obtain the tissue samples and subsequent preparation and analysis of histological slides. Results In the slide microscopy, the control group presented normal aspects. In experimental groups, exacerbation of inflammation was observed, there was a increased thickness of intra-alveolar septa, reduced alveolar lumen, areas of ciliary loss, and neovascular formation. And as the animals' exposure to smoke was extended, the progressive exacerbation of these pulmonary changes was noted. Conclusions The exposure to waterpipe smoke stimulates inflammation and cellular changes in lung tissues of Swiss mice and suggests that the longer the animals' exposure period, the more exacerbated this picture will appear.