Apolipoprotein A-I (apo A-I) represents the main component of the Trypanosome lytic factor (TLF) which contributes to the host innate immunity against Trypanosoma and Leishmania. These parasites use complex and multiple strategies such as molecular mimicry to evade or subvert the host immune system. Previous studies have highlighted the adaptation mechanisms of TLF-resistant Trypanosoma species. These data might support the hypothesis that Leishmania parasites (amastigote forms in macrophages) might express apo A-I to bypass and escape from TLF action as a component of the host innate immune responses. The anti-inflammatory property of apo A-I is another mechanism that supports our idea that apo A-I may play a role in Leishmania parasites allowing them to bypass the host innate immune system.