Sexual dimorphism in the immune systems of females and males is well established. The sex-dependent differences between female and male normal and autoimmune responses is generally attributed to the influence of estrogens and androgens even though limited information has been reported on the specific mechanisms of steroids on immune cells. In general terms females have a greater resistance to various bacterial and viral infections than males with their other enhanced immune capabilities might contribute to their higher survival rates. Macrophages are versatile cells whose activities are programmed by environmental signals. The evidence accumulated to date supports the postulate that sex hormones profoundly influence host defense by controlling the ability of macrophages to participate in immune responses. In the present study, we investigated the direct effect of sex hormones on murine bone marrow derived-macrophages (BMMs) and on leishmania donovani (L.D) infection of Ana-I. It may provide a basis for sex-associated differences in numerous infectious diseases.Methods: Four weeks old female mice of strain C57BL/6j were anesthetized with ether and killed. Then the bone marrow cells were cultured in the presence of M-CSF for 5 days to induce macrophages differentiation and maturation. The resulting bone marrow derived-macrophages(BMMs) were treated with testosterone (10nM, 100nM, 400nM) on the same volume of ethanol in order to induce apoptosis, and cyproterone was added to prevent the apoptosis. Apoptosis of BMMs were detected by DNA fragment assay. Ana-I were infected with promastigotes of L.D at a ratio of 10:1 promastigotes per macrophage after incubated with testosterone(10nM, 100nM) or 17-b-estradiol( 10nM,100nM), separately, for24hours. Giemsa staining monitered the infection rates and infection levels of different time points(0.1h,03h,6h, 12h,24h post infection). Values were analyzed using the SPSS 10.0 for windows software. P-values less than 0.05 were considered statistically significant.Results: There was apoptotic DNA fragmentation in 5-day old BMMs deprived of M-CSF for 24 hours, which demonstrates thatBMMs cultured in the absence of M-CSF were undergoing apoptosis. DNA fragment assay also indicated that testosterone (400nM) in vitro induced apoptosis of BMMs. Cyproterone could inhibit testosterone-induced apoptosis. Ana-I from testosterone-treated groups (100nM) showed an increase in the uptake of parasite (24h post infection, P<0.05) and carried heavier infection rates (12h and 24h post infection, P<0.01) than controls. 17-b-estradiol did not show any influences on L.D infection of Ana-I.Conclusion: Testosterone directly induced apoptosis of BMMs, which could be prevented by androgen inhibitor cyproterone. Serum starvation is known to induce apoptosis in a variety of cell types, and in accordance with this, removaL of M-CSF resulted in apoptosis. Testosterone could enhance the infectivity of L.D to macrophages.