To establish a novel murine model conducive to simian immunodeficiency virus (SIV) replication in vivo, male BALB/c nude mice, aged three weeks, were administered a single intraperitoneal inoculation of SIV-infected MT-2 cells (derived from human T-cell leukemia). Subsequently, alterations in plasma viral load and the engraftment of MT-2 cells in vivo were examined, while immunological changes were assessed via ELISA and flow cytometry analysis. All of the mice in the experimental group exhibited detectable plasma viral loads in their peripheral circulation, largely due to the proliferation of SIV-infected MT-2 cells within the T-cell-deficient environment of nude mice, resulting in colonization of the abdominal cavity and lymph nodes and the subsequent release of free virions to perpetuate the infection. Mice that received highly active anti-retroviral therapy (HAART) treatment demonstrated a statistically significant reduction in plasma viral loads, with HAART administration partially reversing the course of SIV-induced immune dysfunction. Therefore, the model presented in this study offers substantial potential as a robust tool for evaluating antiviral efficacy and immune modulation in an in vivo setting.