Objectives. We found that activation of the nicotinic acid receptor GPR109A, expressed by the MIN6 murine pancreatic β cell line, inhibits nitric oxide accumulation induced by IFN-γ and TNF-α, implicating an anti-inflammatory effect of GPR109A in MIN6 cells. Nevertheless, the mechanism of its anti-inflammatory effect is still unknown. In this study, we used palmitic acid to stimulate MIN6 cells to induce inflammatory cytokine production and explored the mechanism by which GPR109A exerts anti-inflammatory effects. Materials and Methods. RT-PCR and immunocytochemical staining were used to detect the expression of GPR109A in MIN6 cells. Western blotting was used to detect the activation of the Akt/mTOR signaling pathway and expression of the inflammatory cytokine INF-γ, in MIN6 cells, following treatments with palmitic acid and palmitic acid+nicotinic acid, or with different concentrations of nicotinic acid and 3-hydroxybutyrate. Results. In MIN6 cells, GPR109A transcripts and protein are expressed and GPR109A protein is mainly located in the cell membrane and cytoplasm. Palmitic acid enhanced the phosphorylation of Akt and p70S6K and elevated the expression of IFN-γ. Co-treatment with nicotinic acid, which is an agonist of GPR109A, inhibited the palmitic acid-induced phosphorylation of Akt, mTOR, and p70S6K, as well as the expression of IFN-γ. Conclusions. GPR109A may inhibit inflammatory cytokine production, induced by palmitic acid, by MIN6 cells possibly via inhibiting the Akt/mTOR signaling pathway.