Cyclic-nucleotide phosphodiesterases (PDEs) represent a superfamily of enzymes playing a pivotal role in cell signaling by controlling cAMP and cGMP levels in response to receptor activation. PDE activity and expression are linked to many diseases including inflammatory diseases. In light of their specific biochemical properties, PDE inhibition has attracted the interest of several researrs In this context, PDE4 inhibition induces anti-inflammatory effects. Piclamilast and rolipram, well-known PDE4 inhibitors, are endowed with common side effects. The selective phosphodiesterase 4B (PDE4B) inhibitors could be a promising approach to overcome these side effects. In the present study, six potential PDE4B inhibitors have been investigated. Through this study, we identified three PDE4B inhibitors in human macrophages activated by lipopolysaccharide. Interestingly, two of them reduced reactive oxygen species production in pro-inflammatory macrophages.