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We examined the effects of an herbal formula, WL2, on weight loss, lipid metabolism, and associated angiogenesis status. Male SD rats were pre-fed a high-calorie-diet (HCD) for 6 wks to prior establish obesity. Obese rats were randomized to receive vehicle or WL2 (1.5 g/kg) by gavage for 10 wks. Reduced BW was seen with WL2 at Wk 2 and later weeks (p<0.05∼0.01). At Wk 10, BW and weight of abdominal fat pad and the liver were reduced with WL2 by 5.6%, 38% & 13% (p<0.01). Size and total number of adipocytes were reduced with WL2, represented by increased adipocyte number per microscopic view field and reduced total DNA in fat pad (p<0.05). Plasma LDL-c, VEGF, leptin, and adiponectin was decreased with WL2 by 39%, 33%, 35% & 27%, while HDL-c and glucagon increased by 18% & 17% (all p<0.01). Reduced liver weight associates with improvement of hepatic fatty degeneration and steatohepatitis (p=0.006). Gene expression array displays multiple changes in gene expression in many tissues, suggesting enhanced thermogenesis and adipocyte apoptosis, optimized glucose-lipid-protein metabolism, and improved muscle cell survival. In conclusion, WL2 intervention reduces BW and improves energy-glucose-lipid metabolism in DIO through multiple metabolic pathways. The reduced mass of adipose tissue associates with reduction of circulating leptin and adiponectin, inhibition of angiogenesis and optimization of multiple metabolic systems. [ABSTRACT FROM AUTHOR]