The mucosa around implants and the gingiva around teeth respond to plaque formation with the development of an inflammatory lesion which has similar magnitude and histological features. Different cell types in inflamed and healthy periodontal and peri-implant tissues are capable of producing a variety of important pro-inflammatory and anti-inflammatory cytokines and growth factors which mediate the host response. The aim of this study is to compare the expression levels of anti-inflammatory cytokines detectable in the peri-implant soft tissue of two single-implant crowns supported either by zirconia or titanium abutments. Two frozen samples of peri-implant soft tissue of two single-implant crowns supported either by zirconia or titanium abutments were treated to obtain mRNA. The mRNA extracted from these specimens was converted in cDNA and analyzed with “SuperArray GEArray Q Series Human Inflammatory Cytokine/Receptor Gene Array kit”, planned for studying 96 genes involved in inflammatory response. Data showed that gene expression levels of anti-inflammatory cytokines were higher in specimens sampled from the zirconia abutment compared with those from the titanium abutment. It was considered important to detect the mRNA levels of the anti-inflammatory mediators in healthy peri-implant tissues to verify the biological tolerability of zirconia compared with titanium abutments. The difference detected in cytokine expression could be due to the intrinsic biological tolerability of zirconia ceramics or to a lesser bacterial accumulation.