Control of vector sand flies (SFs: Phlebotomus papatasi) and the prevention of leishmaniasis, a major health problem in endemic areas worldwide, has not been successful using current methods. We have conducted control methods in the laboratory that targets the sand rat (Psammomys obesus), a major reservoir host in Israel, Iraq, and other Middle Eastern and North African countries. Five groups of sand rats were treated in the laboratory by feeding endectocides (ivermectin or doramectin), or topically with insecticides (permethrin or deltamethrin). The controls ate normal laboratory sand rat diet. After 2 or 3 weeks of treatment, they were anesthetized and challenged with naïve, non-blood-fed, uninfected female SFs every two weeks for 10 weeks. For each treatment group, adult SF mortality, fecundity, egg hatch, immature SF development, and F1 adult emergence were recorded. Both ivermectin and doramectin caused significant decreases in the number of eggs laid with no survival of the ivermectin 1st instar larva at 8 days post emergence. Doramectin caused significantly more mortality in the blood-fed SFs, less fecundity, less egg hatch, and a significant decrease in F1 adult emergence. The results of the topical treatments and future field testing will be discussed.