This study demonstrates the action of selamectin in the midgut of Rhipicephalus sanguineus females after 48 h of feeding. For this purpose, commercial selamectin was diluted in distilled water to concentrations of 50% and 80%. These dilutions were applied on the back of the hosts in the treatment groups I and II (TI and TII, respectively). Distilled water alone was applied on the control group. Selamectin caused stratification and disruption of the intestinal epithelium, altering the morphophysiology of generative and digestive cells, leading to death. In the TI group (50% solution), the generative cells showed increased mitotic activity presumably as a response to the product action, replacing dead cells. In group TII (80% solution), mitosis were not detected, but there was a greater accumulation of digestive cells with brownish granules in the midgut lumen, possibly a result of oxidation of granules. More digestive cells were observed in the midgut lumen of group TII ticks. These cells get detached from the basal membrane probably to remove the chemicals from the tick’s system (detoxification). The death of generative cells appear to have affected the epithelial cell replacement (formation of new digestive cells), which in turn impaired the blood digestion, the feeding process and the consequent development of the tick. In addition, this study shows that lower concentrations than that specified by the manufacturers of the product, Revolution^® - Pfizer were sufficient to cause drastic cell alterations, inhibiting the viability of exposed ticks.