ObjectiveTo investigate the role of p38 and ERK1/2 during rhesus monkeys mesenchymal stem cells differentiated into neuron-like cells.MethodsTo induce the neuronal phenotype,rhesus monkeys mesenchymal stem cells were maintained in sub-confluent cultures in serum-contain medium supplement with Sonic hedgehog.Western blot analysis the change of p38 and ERK1/2 during rhesus monkeys mesenchymal stem cells differentiated into neuron-like cells.Under transmission and scanning electron microscope,ultra-structure of the differentiated cell were observed.ResultsDuring BMSCs differentiated into neuron-like cells by SHH,Mitogen-activated protein kinases (MAPK) involved in their signal transduction,p38 was activated and ERK1/2 was inhibited.P38 inhibitor SB203580 increased induced differentiation time compared with normal induced cells,and inhibited neurite outgrowth.ConclusionActivation of p38 and inhibition of ERK was impacted on differentiation into neuron-like cells from rhesus monkeys mesenchymal stem cells induced by Sonic hedgehog,which may has potential application on neuroprotection of stem cells in Nervous system diseases