background. Tattoo removal is a common request in dermatologic surgery practices. Conventional tattoo removal modalities consist of mechanical, chemical, and thermal methods, but these interventions may result in undesirable dermal damage, disfiguring scars, and pigmentary changes.objective. To evaluate the efficacy of topical imiquimod and tretinoin for the removal of tattoos in a guinea pig model.methods. Five albino guinea pigs (A–E) were tattooed with black, red, green, and yellow. Beginning 6 hours after tattooing, A received no treatment, B was treated with petrolatum, C had imiquimod cream alternating with tretinoin gel, D had imiquimod cream alone, and E received tretinoin gel alone. The animals were treated for 7 days. Biopsies of the tattoos were taken at 6 hours, 7 days, and 28 days.results. Control guinea pig B had normal-appearing tattoos with consistent histopathology on day 28. Guinea pig D, treated with imiquimod cream clinically, had no visible tattoo, consistent with greatly diminished or no dye evident on histopathology. Guinea pig E, treated with tretinoin gel, and guinea pig C, treated with combination tretinoin gel and imiquimod cream, had faded tattoos and moderate clearance of pigment on histopathology.conclusion. In the guinea pig, the use of imiquimod was successful as a nonsurgical method of acute-phase tattoo removal, but was associated with fibrosis and the loss of dermal appendages.