INTRODUCTION: Mesotherapy is widely used to reduce localized body fat through the subcutaneous injection of lipolytic substances, such as sodium deoxycholate (DEOXI). DEOXI is a biliary salt that dissolves and emulsifies fat, although there is a lack of evidence regarding its safety in the literature. OBJECTIVE: To investigate short-term cardiometabolic effects of a single subcutaneous DEOXI injection on female Swiss mice. METHODS: CEUA approval nº 1011/2017. Four months-old female Swiss mice received one subcutaneous injection of 100 uL of saline (control), 13 ug (D13) or 130 ug (D130) of DEOXI into the right inguinal region. Mice were euthanized 6h, 24h or 7 days after the procedure. Body mass, food intake, serum analytes (glucose, triacylglycerol [TG], glycerol, total cholesterol (TC), HDL cholesterol and liver enzymes) were analyzed. Tissue TG and glycerol were measured int the left ventricle (LV), liver, and brown adipose tissue (BAT). Histopathology and morphometry were performed in the inguinal white adipose tissue (iWAT), BAT and liver. RESULTS: DEOXI did not change body mass and the weight of the collected tissues. Serum TG was higher in D13-6h compared to C-6h (+33,0%, P<0,05). Serum glycerol of D130 were 62,0% lower (P<0,01) in 6h, and 48,7% lower (P<0,05) in 24h vs. C-6h e C-24h, respectively. At 7 days, glycerol of D13 was lower than D13-6h (49,7%, P<0,01). HDL-c was elevated at all times in the D130 group vs. C e D13. TGO was elevated at 24h compared to D13 and C group (+45,7%, P<0,05), and D130 group vs. D13 (-28,4%, P<0,05). TGP was elevated in D13 group at all times. In the iWAT, there was acute inflammation and tissue remodeling. In the BAT, TG was +130,2% higher (P<0,05) in D130-6h, and +80,2% higher (P<0,01) in the D130-24h compared to control. BAT morphometry did not show significant changes between groups. In the liver, tissue TG in the D13-6h was higher than C-6h (+131,6%, P<0,001) and D13-6h (+108,1%, P<0,01). At 24h, hepatic TG of D13 was higher than C-24 (+195,0%, P<0,001) and D13-6h (+126,6%, P<0,001). At 7 days, liver TG of D13-7days group was higher than C-7days (+188,5%, P<0,0001) and D13-6h (+70,0%, P<0,05). Hepatic glycerol of D130-24h was lower than C-24 (-48,6%, P<0,05) and D130-6h (-55,0%, P<0,05), at 7 days was lower in D13-7days (-76,8%, P<0,001) compared to C-7dias and D130-6h (-77,9%, P<0,01). Liver morphometry showed a reduction of hepatocyte density per area in D13-24h, D130-24 and D130 groups compared to control. LV glycerol in D130-6h group was higher than C-6h (+204,8%, P=0,001) and D13-6 (+56,2%, P<0,05). DISCUSSION AND CONCLUSIONS: A single subcutaneous injection of DEOXI leads to both local and systemic changes, in the blood and in metabolically active tissue.