Lipocalin-2 (LCN2) is a novel adipokine with potential roles in obesity, insulin resistance, and inflammation. The aim of the present work was to evaluate the effect of obesity on circulating concentrations and gene and protein expression levels of LCN2 in human visceral adipose tissue (VAT) as well as its involvement in inflammation. VAT biopsies from 47 subjects were used in the study. Real-time PCR and Western-blot analyses were performed to quantify levels of LCN2 in VAT as well as the association with other genes implicated in inflammatory pathways. Forty-four serum samples were used to analyze the circulating concentrations of LCN2. Zymography analysis was used to determine the activity of matrix metalloproteinase (MMP) in VAT. Obese patients exhibited increased mRNA (p < 0.0001) and protein (p = 0.017) expression levels of LCN2 compared to lean subjects. Although no differences in plasma LCN2 concentrations were observed, increased circulating LCN2/MMP-9 complex levels were found (p = 0.038) in the obese group. Moreover, obese individuals showed increased (p < 0.01) activity of MMP-2 and MMP-9/LCN2 complex, while a positive correlation (p < 0.01) between MMP-2 and MMP-9 activities and BMI was observed. Gene and protein expression levels of LCN2 in VAT were positively associated with inflammatory markers (p < 0.01). These findings represent the first observation that mRNA and protein levels of LCN2 are increased in human VAT of obese subjects. Furthermore, LCN2 is associated with MMP-2 and MMP-9 activities as well as with pro-inflammatory markers suggesting its potential involvement in the low-grade chronic inflammation accompanying obesity.