Microglial activation plays an integral role in the development and course of neurodegeneration. Although neuropeptides such as bradykinin (BK), somatostatin (SST), and endothelin (ET) are known to be important mediators of inflammation in the periphery, evidence of a similar function in brain is scarce. Using immunocytochemistry, we demonstrate the expression of receptors for BK (B1, B2 subtypes), ET (ETA, ETB subtypes) and SST (SST 2, 3, 4 subtypes) in primary microglia and microglial cell lines. Exposure of BV2 and N9, as well as primary microglial cells to BK or SST increased AΒ uptake in a concentration-dependent manner, whereas endothelin decreased AΒ uptake. This was caused by increased phagocytosis of AΒ since the rate of intracellular AΒ degradation remained unaffected. All neuropeptides increased chemotactic activity of microglia. In addition, BK reduced AΒ-induced expression of proinflammatory genes including iNOS and COX-2. ET decreased the AΒ-induced expression of monocyte chemoattractant protein 1 and interleukin-6. These results suggest that neuropeptides play an important role in chemotaxis and AΒ clearance and modulate the brain's response to neuroinflammatory processes.