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We have found that triggering receptors expressed on myeloid cell-2(TREM-2) has a strong antiinflammatory effect.Vasoactive intestinal peptide (VIP) can regulate expression of cytokines and receptors.We further discuss VIP whether regulate the TREM-2 expression of LPS induced macrophages.Objective: To study effect of VIP on TREM-2 expression.Methods: TREM-2 expression was detected by RT-PCR and flow cytometry.Results: (1) VIP can up-regulated TREM-2 expression of LPS-induced macrophages.(2) The signal pathway blockers (H-89 and PD98059) can reverse the effect of VIP (3) AP1 may be one of the core transcription factors of TREM-2 expression, and VIP could increase AP1 expression.Conclusion: VIP up-regulated AP 1 expression through PKA and ERK signaling pathways, then TREM-2 expression was increased, and finally block the waterfall reaction of inflammatory mediators.