Background: T. gondii is an intracellular protozoan parasite that can establish a latent infection in the central nervous system that may develop into chronic inflammation resulting in neurobehavioral problems in the host. The processes behind these alterations are still largely mysterious. Objective: Detection of behavioral, histopathological and immunohistochemical changes in mice infected by T. gondii Me49 strain. Material and Methods: A total of 105 adult male Swiss albino mice were divided into 60 used for experimental infection, and 45 as control. Assessment of physical appearance was monitored for acute toxoplasmosis daily for three weeks post infection (PI). Correlation between behavior changes and the degree of infection was conducted by measuring histopathological (H&E and silver stain) and immunohistochemical (presence or absence of CD3, CD138 and caspase-3 immunoreactive cells) parameters weekly starting from 7th week to the 12th week PI. Results: Infected mice had neurobehavioral problems. Variable degrees of perivascular and interstitial inflammatory infiltrates, astrocytosis, deteriorated neurons, and meningitis were demonstrated by histopathology when compared to uninfected controls. Inflammatory cells (mainly lymphocytes) entered the parenchyma at mild, moderate, and severe levels in the brains of infected mice. Immunohistochemical assessment of CD3, CD138 and caspase-3 revealed a substantial increase in CD3 expression by clusters of activated astrocytes in the cerebral parenchyma, suggesting an increase in astrocyte numbers and function that was progressive over time. CD138 and caspase-3 immunoreactivity showed decreased expression by the activated astrocytes. Conclusion: Chronic toxoplasmosis causes deterioration in cognitive and emotional behavior of the infected host, resulting in neuropsychiatric and behavioral disturbances.