Abstract Vascular growth is a prerequisite for adipose tissue (AT) development and expansion. Some AT cytokines and hormones have effects on vascular development, like vascular endothelial growth factor (VEGF- A), angiopoietin (ANG-1), ANG-2 and angiopoietin-like protein (ANGPTL-4). In this study we investigated the independent and combined effects of diet-induced weight loss and exercise on AT gene expression and proteins levels of those angiogenic factors. Seventy-nine obese males and females were randomized: 1. Exercise-only (EXO; 12-weeks exercise without diet-restriction), 2. Hypocaloric diet (DIO; 8-weeks very low energy diet (VLED) + 4-weeks weight maintenance diet) and 3. Hypocaloric diet and exercise (DEX; 8-weeks VLED + 4-weeks weight maintenance diet combined with exercise throughout the 12 weeks). Blood samples and fat biopsies were taken before and after the intervention. Weight loss was 3.5 kg in the EXO group and 12.3 kg in the DIO and DEX groups. VEGF-A protein was non-significantly reduced in the weight loss groups. ANG-1 protein levels were significantly reduced 20-25% after all three interventions (p<0.01). The ANG-1/ANG-2 ratio was also decreased in all three groups (p<0.05) by 30-38%. ANGPTL-4 was increased in the EXO group (14%, p<0.05) and 9% (p<0.05) in the DIO group. VEGF-A, ANG-1, and ANGPTL-4 were all expressed in human AT, but only ANGPTL-4 was influenced by the interventions. Our data show that serum VEGF-A, ANG-1, ANG-2 and ANGPTL-4 levels are influenced by weight changes, indicating the involvement of these factors in the obese state. Moreover, it was found that weight loss generally was associated with a reduced angiogenic activity in the circulation.