Microglia are the primary immunocompetent cells that protect the brain from environmental stressors; however, their activation can also have deleterious effects on brain functioning. Indeed, environmental toxins and microbial agents can induce microglial driven inflammatory processes and induce a cytotoxic environment. Recent therapeutic strategies have sought to determine how to modulate microglia, to favour their neuroprotective effects, while minimizing toxic outcomes. We hypothesized that BDNF would have a modulatory effect on inflammation in isolated microglia cultures in the context of a bacterial endotoxin. It was found that a BDNF treatment following LPS-induced inflammation blunted the release of both IL-6 and TNF-α in primary microglia. In neurons, LPS-activated microglial media was able produce an inflammatory effect to some extent, and again, BDNF treatment attenuated this effect. We speculate that BDNF plays a role in regulating microglia activation and localized microglia-neuron crosstalk may be crucial in preventing damaging effects of inflammatory mechanisms.