Exposure to metal arsenic (As) has been proposed as a risk factor for autism spectrum disorders (ASDs), which are neurodevelopmental disorders with worldwide increasing in its incidence. In the present study, BTBR T +  tf /J (BTBR) mice with ASD-like behavioral characteristics and control highly social FVB mice were orally exposed to 0.1 mM arsenic(III)oxide for 4 weeks, and were compared to investigate neuroimmunological or behavioral abnormalities. IgG1:IgG2a ratios in brain tissues from BTBR mice exposed to As (BTBR-As) were significantly higher than those of BTBR-control mice (BTBR-C), but this change did not occur in FVB mice exposed to As. Levels of IL-4, IFN-γ, IL-1β, IL-17, and TNF-α in brain tissue were lowered in BTBR-As relative to BTBR-C, but this tendency was not observed with FVB mice. BTBR-As mice demonstrated decrease in relative travel distance and time spent in the center vs. the periphery of open field arena compared to BTBR-C. Sociability evaluation using three-way chamber test did not clearly demonstrate As-mediated alteration in social interaction in BTBR mice. These findings suggest the potential for As-driven predominant T H 2-like reactivity profile in the brain microenvironment of BTBR mice and for As-mediated locomotive impairment probably associated with ASD.