Lipopolysaccharide (LPS) has a negative impact on long-term potentiation (LTP) in the rat hippocampus, which has been correlated with increased concentration of interleukin-1 beta (IL-1 beta) and activation of p38 and c-Jun N-terminal kinase (JNK). It has been documented that phosphatidylserine (PS)-containing liposomes induce anti-inflammatory signals and we report that pre-treatment of rats with PS liposomes prevented these LPS-induced effects while also inhibiting microglial activation. We also observed increased concentration of the anti-inflammatory cytokine interleukin-10 (IL-10), whose intracerebroventricular injection administration mimicked the effects of PS liposomes on LTP. This suggests that administration of PS liposomes protects against the deleterious effects of LPS possibly through generation of the anti-inflammatory cytokine IL-10.