Background　The potential toxicity is a well-known side effect of local anesthetics （LA） which is widely used in nerve block and analgesia. The mechanisms of local anesthetic toxicity were further investigated.　Objective　This review summarized the recent studies examining the mitogen-activated protein kinases （MAPKs） signaling pathway and their regulation， and discussed the effects of MAPKs on neurotoxicity of LA.　Content　Accumulating evidences indicate that neurotoxicity of LA is related to apoptosis. MAPKs， a serine-threonine protein kinase family， play a crucial role in apoptosis of cells. So that the effects of MAPKs signaling pathway on neurotoxicity of LA is becoming a hot issue to be researched. And the impact of extracellular signal-regulated kinase （ERK）， c-Jun N-terminal kinase （JNK）， p38MAPK are more concerned.　Trend　The MAPKs signaling pathway and their regulation play an important part in the underlying mechanisms of local anesthetic neurotoxicity which could provide evidences and theory for clinical use of LA.