Abstract: Killed Leishmania Vaccine (KLV) has been applied for its immunogenicity in hosts. Imiquimod (IMQ) as adjuvant induces immune responses during leishmaniasis. In this study, KLV/IMQ were applied to inhibit the proliferation and visceralization of Leishmania major in mice. Animals were treated with KLV/IMQ, then they infected by promastigotes of L. major. Six weeks later, a small nodule was appeared leading to a large lesion and visceralisation. KLV/IMQ effects on physiopathology, lesion sizes, lesion delay, amastigote proliferation and leishmania detection in target organs were all studied. Data analysis of body weight, hepato/splenomegaly and survival rates indicated no significant differences among experimental groups. It is concluded that KLV/IMQ represented no cytotoxic effects but they partly had effects on lesion size and impressed number of amastigotes inside macrophages. Application of KLV/IMQ decreased visceralization in liver; induced NO in liver, spleen and plasma. Although, IMQ application solely decreased visceralization in lymph nodes but KLV/IMQ increased SGOT/SGPT, however they represented no effects in concentrations of plasma Cu/Zn. Unlike IMQ topical application, its injection presented no ameliorative affects on CL, however its inhibition systemic leishmaniasis is indicated here. IMQ efficacy may be associated with route, dose and number of injection, which require more investigations.