A model of murine toxoplasmosis was used to study cellular and temporal expression of uncoupling protein-2 (Ucp2) in the brain. In situ hybridization indicated that Ucp2 was located in neurons. Nuclei structures involved in energy balance, in particular the nucleus of the solitary tract (NST), was shown to have a positive association between negative energy balance and Ucp2 levels. Infection-induced Ucp2 expression colocalized mainly with microglial cells, but also with infiltrating macrophages and neutrophils in the brain, which was evident from day 9 post-infection. Using cytokine knockout mice we demonstrate that microglial Ucp2 induction in the brain was largely dependant on interferon-gamma, but not interleukin-6 or tumour-necrosis-factor-alpha in response to infection. In summary, this study shows that Ucp2 is regulated in a different manner in neurons than in microglia/phagocytes following infection. Our study indicates that an association exists between negative energy balance and neuronal Ucp2 levels in the NST, in particular.