OBJECTIVE Acute decompensated heart failure is often treated with a combination of loop and thiazide-like diuretics. Of these thiazide-like diuretics, two common choices are intravenous chlorothiazide or oral metolazone. Metolazone is more potent and has a longer duration of action, but since it is an oral formulation, it has a longer on-set time as compared to chlorothiazide. In addition, metolazone is poorly water-soluble, thereby rendering intravenous formulation more challenging. To address these issues, we proposed the formulation of a solvent-free metolazone emulsion for intravenous administration. METHODS An oil-in-water emulsion containing 1 mg/mL of metolazone was formulated by homogenizing soybean oil and l-lecithin in water in the presence of optimized concentrations of glycerin with tween 80 or poloxamer 188 as surfactant. The emulsion was characterized on the basis of particle size, zeta potential, morphology and metolazone release kinetics. The diuretic effect of the metolazone emulsion was evaluated in rats. RESULTS The 1 mg/mL metolazone emulsion prepared with 5% tween 80 displayed the best physical stability. The emulsion exhibited a hydrodynamic diameter of 157.13±1.52 nm. About 93% of metolazone was released from the formulation within 2 h. The 2 mg/kg and 4 mg/kg dose of the metolazone emulsion increased urine output in the rats by 68.9 and 134%, respectively, as compared to control rats. Furthermore, the 4 mg/kg dose exhibited a 168.8%, 25.8%, and 150.9% increase in sodium, potassium, and chloride, respectively. CONCLUSIONS This metolazone emulsion was capable of increasing urine volume output and demonstrated both natriuretic and kaliuretic properties.