There has been an increasing interest in organoselenium chemistry and biochemistry since several of these compounds possess antioxidant activity. Amongst them, diphenyl diselenide (DPDS) has been the focus of this study. We evaluated the antioxidant properties of DPDS in cultured macrophages (Mph). First, we determined the toxicity of DPDS by means of the trypan blue exclusion assay. We found that DPDS diminished the percentage of viable cells in non-stimulated Mph at concentrations higher than 5¦ÌM, whereas it did not induce any change in the viability of the LPS stimulated cells. Then, we evaluated whether DPDS inhibited the production of nitric oxide (NO), an inflammatory mediator which can be harmful to the host tissue. We observed that the addition of DPDS decreased the production of NO in a dose dependent manner in both conditions tested. Next, we analyzed the enzyme iNOS that produces NO from arginine. We found that DPDS induced a diminution of iNOS in the cells in basal conditions but not in the cells activated with LPS, suggesting that another regulation mechanism could exist. Finally we observed that DPDS affected the antigen presentation capacity of Mph since DPDS induced a diminution of the percentage of MHCII+ and CD86+ cells. These results suggest that DPDS could be an interesting anti-inflammatory compound to implement in the therapy of autoimmune inflammatory diseases.