It is well known that both selective serotonin and serotonin noradrenaline reuptake inhibitors can improve the symptoms major depressive disorder to increase the concentration for monoamine in the synaptic cleft based on the monoamine hypothesis. However, accumulating evidence has indicated that inflammation in the brain may be a key factor in the pathophysiological mechanisms of developing symptoms of major depressive disorder. In this study, we focused on whether duloxetine can show the ameliorative effect for inflammatory response induced by lipopolysaccharide (LPS) in BV-2 microglial cells. Our results indicated that duloxetine decreased the NO production induced by LPS in a concentration-dependent manner. The increase in the protein expression level of iNOS by LPS was decreased in a concentration-dependent manner by duloxetine treatment. Moreover, the increase of the protein expression levels of phosphorylated-IκBα, phosphorylated-Akt and Akt by LPS were also decreased. Unexpectedly, the protein expression levels of other pro-inflammatory factors such as COX-2 and phosphorylation ratios for various molecules including IκBα and Akt were not altered by the treatment of duloxetine. These findings suggest that duloxetine may also act as an anti-inflammatory agent, which could contribute to its therapeutic effectiveness.