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Leishmania (L.) tropica is the causative agent of different forms of human leishmaniasis. There is little information about the role of Leishmania-specific antibodies in the immune response against L. tropica infection. The aim of this study is to evaluate the role of Leishmania-specific antibodies and their immunoglobulin G (IgG) isotypes in L. tropica infection. Methods: L. tropica at two different doses (high dose, 106 parasites/mouse and low dose, 103 parasites/mouse) were used for infection of BALB/c mice. BALB/c mice infected with Leishmania major were used for comparison. Anti-Leishmania antibodies of the IgG1 and IgG2a isotypes were assayed by enzyme-linked immunosorbent assay. Results: Our data showed that (1) a higher parasite dose results in higher levels of antibody. (2) L. tropica infection results in a lower IgG1 antibody response, compared with L. major infection. (3) The IgG2a/IgG1 antibody response in L. tropica infection is higher than that in L. major infection. Conclusion: A higher IgG2a/IgG1 ratio is associated with protective immune response in L. tropica infection. These data can help to approach the complex profile of immunity against L. tropica infection.