Introduction and purpose: Leishmaniasis are neglected diseases that are endemic in more than half of the provinces of Iran. The causative agent of this disease is Leishmania protozoa and its transmission to human is through the bites of phlebotomine sand flies. This study reviews the growth and development of Leishmania in the body of sand flies at the molecular level. Methods: In this study a narrative review was carried out. The corpus was collected by searching the keywords of Leishmania, sand fly, phlebotomus, lutzomyia in the databases of PubMed, Scopus, SID, Web of Science, Ovid Medline, and Google Scholar search engine. The studied articles were those which has been published on the interaction between the sand fly vectors and Leishmania parasite until 2018. Results: The parasites grow when they encounter natural barriers in the body of the sand flies, including proteolytic enzymes, peritrophic membrane, excretion of the digestive system, and immune system in sand fly vectors. Attachment of Leishmania to sand fly digestive tract determines the ability of sand fly to support the development of parasite, which leads to the transmission of leishmaniasis.Conclusion: Studies on the development and life cycle of Leishmania within the body of sand flies are of utmost importance due to the spread of leishmaniasis in Iran and the world, difficulty in their control, and lack of effective vaccine products against leishmaniasis. The findings of the current study aimed at identifying and enhancing the natural barriers to the development of Leishmania in sand fly vectors and introducing new strategies for the control of leishmaniasis.