Response surface based on Box-Behnken design was used to investigate and optimize the reaction conditions for conversion of neem seed oil in to biodiesel. The oil was extracted from the seed using n-hexane and trans esterified using methanol and sulfated zirconia catalyst to biodiesel. The oil extracted and biodiesel produced were analyzed for physicochemical and fuel properties using ASTM methods and are in conformity with ASTM D6751. The fatty acid methyl ester was estimated using Gas Chromatography- Mass Spectrophotometry (GC-MS). The results obtained showed percentage oil yields of 40.64 ± 1.01%. The optimum yield of 89% was obtained at the reaction temperature, reaction time, molar oil to methanol ratio and catalyst concentration, 60^oC, 1:12, 90 minutes and 1% wt. respectively. The model obtained has good predictive power, Methanol to oil molar ratio and reaction time followed by temperature were the major parameters that determine the response output (biodiesel yield).