Visceral Leishmaniasis is a macrophage associated disorder for the treatment of which antimony based drugs like SAG and SSG were the first choice in the recent past. The clinical value of antimony therapy is now declined against VL because increasing cases of Sodium Antimony Gluconate (SAG) resistance have reached outstanding proportion in Bihar, India. Besides the drugs used also have potential sideeffects on kidneys.  We have  evaluated the effect of combining CD2 with conventional antimonial (sb) therapy in protection in BALB/c mice infected with either drug sensitive or resistant strain of Leishmania donovani with 3 million parasites via-intra-cardiac route. Mice were treated with anti CD2 adjunct SAG sub-cutaneously twice a week for 4 weeks. Assessment for measurement of weight, spleen size, anti-Leishmania antibody titer, T cell and anti-leishmanial macrophage function was carried out day 0, 10, 22 and 34 post treatments.  The combination therapy was shown boosting significant proportion of T cells to express CD25 compared to SAG monotherapy. Although, the level of IFN-γ was not statistically different between combination vs monotherapy (p = 0.298) but CD2 treatment even alone significantly influenced IFN- γ production than either SAG treatment (p = 0.045) or with CD2 adjunct SAG treatment (p = 0.005) in Ld-S strain as well as in Ld-R strain. The influence of CD2 adjunct treatment was also documented in anti-leishmanial functions in macrophages. As shown, the super-oxide generation began enhancing very early on day 10 after SAG treatment with CD2 during which SAG action was at minimum. Our results indicate that CD2, which can boost up a protective Th1 response, might also be beneficial to enable SAG to induce macrophages to produce Leishmanicidal molecules and hence control the infection in clinical situation like Kala-azar . Kidney impairment is the major impedance for disease control but the encouraging results obtained