Methanolysis of muskmelon seed oil was optimized employing RSM (response surface methodology). Four process variables were evaluated at two levels: methanol/oil molar ratio (3:1-12:1), catalyst concentration in relation to oil mass (0.25-1.25. wt KOH), reaction temperature (25-65 °C) and methanolysis reaction time (20-90. min). Multiple regression analysis was employed to get the quadratic polynomial equation for predicting transesterification using RSM. The result indicated that catalyst concentration and reaction temperature were the important factors that significantly affect the yield of MMOMEs (muskmelon oil methyl esters)/biodiesel. The RSM methodology was used to obtain methyl esters yield (89.5) were found at following reaction conditions; 5.8:1 methanol-to-oil ratio, 0.79 catalyst concentration, 55 °C reaction temperature and 72.5-min reaction time. There was a linear correlation between observed and predicted values. The biodiesel was analyzed using GC/MS (gas chromatography/mass spectrometry) which indicated four FAMEs (fatty acid methyl esters) (linoleic-, oleic-, palmitic- and stearic acids) as its major components. The FT-IR (fourier transform infraRed) spectrum of MMOMEs was also acquired to ensure the confirmation of methyl esters formation. Fuel properties of MMOMEs were determined and found to satisfy the ASTM D 6751 and EU 14214 specifications. © 2011 Elsevier Ltd.