Various mouse models to study dengue have been described by different au-thors, some of them using immunodeficient or some using humanized mice. Our group reported previously a deadly murine model, which used the intra-cranial inoculum of highly virulent Dengue virus (DENV) in immune com-petent mouse. Here we present a model of immune competent mouse (C57BL/6), infected subcutaneously by the same highly virulent DENV (DENV3 genotype I). In this immunocompetent systemic mice model, the cytokine levels and hematological parameters such as total and differential leukocyte and platelets counts, together with weight loss, were considered important monitoring parameters, allowing a better understanding of the sys-temic human disease. Mice were inoculated subcutaneously and evaluated by the percentage weight variation as well as the clinical signs. Hematological parameters and cytokines levels were measured and viral titration in brain tissue or serum neutralization was performed to confirm mice infection. The subcutaneously DENV inoculated mice showed weight loss after infection, but they did not show any other clinical signs. The leukocytes and platelets de-creased after subcutaneous inoculation. The cytokines TNF alpha and IFN gamma increased after infection in mice. The subcutaneous model provided scope for improved understanding of the dengue pathogenesis, as well as possible mechanism for protection to subsequent mouse infected by intra-cranial route in mice. This model could be used to study the vertebrate im-mune response and evaluation of drugs or vaccine against dengue virus.