Aim:　Phosphodiesterase　4　(PDE4)　isozymes　are　involved　in　different　functions,　depending　on　their　patterns　of　distribution　in　the　brain.　The　PDE4　subtypes　are　distributed　in　different　inflammatory　cells,　and　appear　to　be　important　regulators　of　inflammatory　processes.　In　this　study　we　examined　the　effects　of　ferulic　acid　(FA),　a　plant　component　with　strong　anti-oxidant　and　anti-inflammatory　activities,　on　lipopolysaccharide　(LPS)-induced　up-regulation　of　phosphodiesterase　4B　(PDE4B)　in　PC12　cells,　which　in　turn　regulated　cellular　cAMP　levels　and　the　cAMP/cAMP　response　element　binding　protein　(CREB)　pathway　in　the　cells.　Methods:　PC12　cells　were　treated　with　LPS　(1　mu　g/mL)　for　8　h,　and　the　changes　of　F-actin　were　detected　using　laser　scanning　confocal　microscopy.　The　levels　of　pro-inflammatory　cytokines　were　measured　suing　ELISA　kits,　and　PDE4B-specific　enzymatic　activity　was　assessed　with　a　PDE4B　assay　kit.　The　mRNA　levels　of　PDE4B　were　analyzed　with　Q-PCR,　and　the　protein　levels　of　CREB　and　phosphorylated　CREB　(pCREB)　were　determined　using　immunoblotting.　Furthermore,　molecular　docking　was　used　to　identify　the　interaction　between　PDE4B2　and　FA.　Results:　Treatment　of　PC12　cells　with　LPS　induced　thick　bundles　of　actin　filaments　appearing　in　the　F-actin　cytoskeleton,　which　were　ameliorated　by　pretreatment　with　FA　(10-40　mu　mol/L)　or　with　a　PDE4B　inhibitor　rolipram　(30　mu　mol/L).　Pretreatment　with　FA　dose-dependently　inhibited　the　LPS-induced　production　of　TNF-alpha　and　IL-1　beta　in　PC12　cells.　Furthermore,　pretreatment　with　FA　dose-dependently　attenuated　the　LPS-induced　up-regulation　of　PDE4　activity　in　PC12　cells.　Moreover,　pretreatment　with　FA　decreased　LPS-induced　up-regulation　of　the　PDE4B　mRNA,　and　reversed　LPS-induced　down-regulation　of　CREB　and　pCREB　in　PC12　cells.　The　molecular　docking　results　revealed　electrostatic　and　hydrophobic　interactions　between　FA　and　PDE4B2.　Conclusion:　The　beneficial　effects　of　FA　in　PC12　cells　might　be　conferred　through　inhibition　of　LPS-induced　up-regulation　of　PDE4B　and　stimulation　of　cAMP/CREB　signaling　pathway.　Therefore,　FA　may　be　a　potential　therapeutic　intervention　for　the　treatment　of　neuroinflammatory　diseases　such　as　AD.