Our study investigated the innate immune response to Toxoplasma gondii infection by assessing microglial phenotypic changes and sickness behavior as inflammatory response markers post-ocular tachyzoite instillation. Disease progression in Swiss albino mice was compared with documented outcomes in BALB/c mice using identical ocular route and parasite burden (2x105 tachyzoites), with saline as control. Contrary to expectations, Swiss albino mice displayed rapid, lethal disease progression, marked by pronounced sickness behaviors and mortality within 11-12 days post-infection, while survivors showed no apparent signs of infection. Comparative analysis revealed T. gondii-infected BALB/c mice exhibited reduced avoidance of feline odors, while in-fected Swiss albino mice showed enhanced avoidance responses. There was a significant increase in microglial cells in the dentate gyrus molecular layer of infected Swiss albino mice compared to BALB/c mice and their respective controls. Hierarchical cluster and discriminant analyses iden-tified three microglial morphological clusters, differentially affected by T. gondii infection across strains. BALB/c mice exhibited increased microglial branching and complexity, while Swiss al-bino mice showed reduced shrunk microglial arbors, diminishing morphological complexity. These findings highlight strain-specific differences in disease progression and inflammatory reg-ulation, indicating lineage-specific mechanisms in inflammatory responses, tolerance, and re-sistance. These elements are critical in devising control measures for toxoplasmosis.