This work reports the chemical composition of the essential oil of Lippia sidoides (EOLS) and evaluation of the topical effect of EOLS and thymol against different irritant agents in vivo. The essential oil was obtained by hydrodistillation, and gas chromatography/mass spectrometry analysis identified the main constituents: thymol (84.9%) and p-cymene (5.33%). The antiinflammatory activity was evaluated using the mouse models of acute ear inflammation induced by croton oil, arachidonic acid, phenol or histamine, and chronic inflammation induced by croton oil. The topical application of EOLS or thymol at a dose of 2 mg/ear significantly reduced (p < 0.001) ear edema induced with arachidonic acid by 45.1% and 47.4% and reduced ear edema induced with phenol by 33.2% (p < 0.05) and 54.7% (p < 0.01) in acute ear edema. However, a proinflammatory effect of EOLS and thymol was evidenced when it was applied for more than 1 day. There were no statistical differences in antiedematogenic activity between EOLS and thymol. In conclusion, the results indicate that thymol is the constituent responsible for the topical antiinflammatory activity of EOLS. Thus, these findings could justify the popular use of L. sidoides by alternative medicine, but chronic use has an inflammatory effect. Copyright © 2012 John Wiley & Sons, Ltd.