It is known that pinitol acts as a mediator of the insulin-signaling pathway, though little is known about its anti-inflammatory effect in human obesity. Therefore, this study aimed to evaluate the effect of pinitol on peripheral blood mononuclear cells (PBMCs) and visceral (VAT) and subcutaneous adipose tissues (SAT), focusing on the involvement of endoplasmic reticulum (ER) stress and sirtuin 1 (SIRT1). In the intervention study, thirteen obese subjects consumed a pinitol-enriched beverage (PEB) for 12 weeks. In the exvivo study, a biopsy of VAT and SAT was removed from thirty-four obese patients and incubated with D-pinitol for 48h. The consumption of a PEB reduced circulating levels of IL6 and TNFα and increased SIRT1 protein expression in PBMCs. Exvivo experiments showed a decline in gene expression and protein levels of IL6 and TNFα in SAT and a reduction in ER stress parameters (ATF6 and CHOP), while VAT markers remained unaltered. Differential gene expression profiles revealed an up-regulation of SIRT1 and insulin-signaling pathways in SAT with respect to VAT. Our results suggests that pinitol down-regulates the inflammatory pathway which may lead to novel treatment options for obesity and its metabolic disorders.