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We investigated the ability of folic acid to modulate the inflammatory responses of LPS activated BV‐2 microglia cells and the signal transduction pathways involved. To this aim, the BV‐2 cell line was exposed to LPS as a proinflammatory response inducer, in presence or absence of various concentrations of folic acid. The production of nitric oxide (NO) was determined by the Griess test. The levels of tumor necrosis factor‐alpha (TNF‐α), interleukin‐1 beta (IL‐1β), and IL‐10 were determined by ELISA. Inducible NO synthase (iNOS), nuclear transcription factor‐kappa B (NF‐κB) p65, MAPKs protein, and suppressors of cytokine signaling (SOCS)1 and SOCS3 were analyzed by western blotting. TNF‐α and IL‐1β, as well as iNOS dependent NO production, resulted significantly inhibited by folic acid pretreatment in LPS‐activated BV‐2 cells. We also observed that folic acid dose‐dependently upregulated both SOCS1 …