N, N-diethyl-m-toluamide (DEET) is a common and fairly safe active ingredient in many insect repellents. Our recent studies showed that when applied to the skin, DEET has a potent anti-parasitic effect against Schistosoma mansoni. However, the beneficial effects of DEET lasted only for a few minutes, presumably due to its rapid absorption through the skin. In this study, we evaluated different carrier formulations that prolong the activity of DEET in the skin. Among the various formulations analyzed, DEET incorporated into liposomes (LIPODEET) appeared to prolong the activity of DEET for more than 48 hr after a single application. Furthermore, LIPODEET was found to be minimally absorbed through the skin and loss due to washing off was limited. These findings thus suggest LIPODEET is a safe and long-acting formulation of DEET that is quite effective against schistosomiasis.