Among the problems associated to leishmaniasis, the two most outstanding ones are the lack of a vaccine and the adverse effects caused by drugs use for its control. Meglumine antimoniate compounds are the first-line drugs in the treatment for cutaneous leishmaniasis (the most prevalent form of the disease in Colombia); nevertheless, they are far from being ideal drugs due to their toxicity (not to mention the emergence of drug-resistant parasites), all of which has prompted current search for new strategies to improve their safety. This work assesses the effectiveness and safety (toxicity including new aspects related with immunotoxicity not reported previously) of two different meglumine antimoniate formulations using an in vitro and in vivo murine model. The results evidence that although both injectable formulations induce an equally efficient (clearance of intracellular parasites), both give rise to adverse effects, including a preferential immunomodulation on Balb/c mice and in a lesser proportion on ICR mice. These results are comparable to human trials reporting variable reactions when following the same treatment regimen. The model presented herein is proposed as a tool for evaluating the effectiveness and safety of meglumine antimoniate-based antileishmanial formulations.