Benzothiazole derivatives are highly interesting molecules for drug development, because they already have been shown to be useful for treating various diseases including neurodegenerative disorders. An inflammation response in the central nervous system mediated by activation of microglia is a key event in the early stages of the development neurodegenerative diseases. We have synthesized and examined various benzothiazole derivatives against to the neuroinflammation. In this study, we have investigated the neuroprotective effects of KHG21834, a benzotiazole derivative, on lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. KHG21834 was a selective inhibitor of proinflammatory cytokine production by activated glia. KHG21834 significantly suppressed the LPS-induced upregulation of tumor necrosis factor-α and interlukin-1β in a dose-dependent manner. The production of inducible nitric oxide synthase (iNOS) was also studied in LPS-stimulated BV-2 cells as a model of microglia activation. KHG21834 dose dependently attenuated nitrite production and iNOS protein expression in LPS-stimulated murine BV-2 microglia. In addition, the neuroprotective effect of KHG21834 was similarily observed in vivo. These results demonstrate a potent suppressive effect of KHG21834 on proinflammatory responses of microglia, suggesting a therapeutic potential for this compound in neurodegenerative diaeases accompanied by microglial activation.