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Objective Hydrogen sulfide is a novel gasotransmitter and has been reported to exhibit anti-inflammatory effects on LPS-stimulated glial cells in our previous study.Here we continued to investigate the role ofACS84, a novel H2S-releasing compound derived from l-dopa, in LPS-induced inflammation in microglia.Methods The microglia were treated with LPS (100 ng/mL) for 24 h to induce inflammation.The levels of nitric oxide in the cell-free culture supernatant were determined by Griess reagent with a commercial kit from Promega.The levels of other pro-inflammatory factors, such as TNF-α, ICAM-1 and IL-6 were measured by ELISA with commercial kits from R&D.The phosphorylation of p38, JNK, ERK1/2 and STAT-3 were analyzed by Western blotting.The cell viability was assessed by MTT method.Results (1) ACS84 suppresses LPS-stimulated iNOS upregulation and NO generation in microglia; (2) ACS84 inhibits LPS-evoked inflammatory cytokines generation in microglia; (3) ACS84 attenuates LPS-stimulated phosphorylation of MAPKs in microglia; (4) ACS84 ameliorates LPS-induced phosphorylation of STAT3 in microglia; (5) ACS84 attenuates the microglia-mediated neurotoxicity on SH-SY5Y cells.Conclusion ACS84 may protect against LPS-induced cell injury via anti-inflammation in MAPK/STAT3-dependent mechanisms and thus it may have therapeutic potential for the treatment of Parkinsons disease.