BACKGROUND The expansion of adipose tissue is linked to the development of its vasculature, which appears to have the potential to regulate the onset of obesity. However, at present, there are no studies highlighting the relationship between human adipose tissue angiogenesis and obesity-associated insulin resistance (IR). RESULTS Our aim was to analyze and compare angiogenic factor expression levels in both subcutaneous (SC) and omentum (OM) adipose tissues from morbidly obese patients (n = 26) with low (OB/L-IR) (healthy obese) and high (OB/H-IR) degrees of IR, and lean controls (n = 17). Another objective was to examine angiogenic factor correlations with obesity and IR.Here we found that VEGF-A was the isoform with higher expression in both OM and SC adipose tissues, and was up-regulated 3-fold, together with MMP9 in OB/L-IR as compared to leans. This up-regulation decreased by 23% in OB/-H-IR compared to OB/L-IR. On the contrary, VEGF-B, VEGF-C and VEGF-D, together with MMP15 was down-regulated in both OB/H-IR and OB/L-IR compared to lean patients. Moreover, MMP9 correlated positively and VEGF-C, VEGF-D and MMP15 correlated negatively with HOMA-IR, in both SC and OM. CONCLUSION We hereby propose that the alteration in MMP15, VEGF-B, VEGF-C and VEGF-D gene expression may be caused by one of the relevant adipose tissue processes related to the development of IR, and the up-regulation of VEGF-A in adipose tissue could have a relationship with the prevention of this pathology. ; Journal Article; Research Support, Non-U.S. Gov't; This work was supported in part by grants from the Andalusian Health Service [SAS PI-0251], from Fondos de Investigación Sanitaria PS09/00997, Instituto Carlos III, from Incentivos a Proyectos de Excelencia p08-CTS-04369. Consejería de Innovación, Junta de Andalucía, and Rajaa El Bekay is recipient of a post-doctoral grant "Miguel Servet" (FIS-2007) (CP07/00288) from the Spanish Ministry of Health; and part of this project was supported by a grant from the Spanish Ministry of Health (FIS) (PI070953), and from Plan Nacional (MEC) SAF2009-09364 and S2010-BMD-2423 from Comunidad de Madrid. CIBEROBN is an initiative of ISCIII (Instituto de Salud Carlos III), Spain.