This work is concerned with application of simple, accurate, precise and highly selective reverse phase high performance liquid chromatographic (RP-HPLC) method for simultaneous estimation of duloxetine hydrochloride (DUL)and methylcobalamin (MCB) in combined dosage form. chromatographi separation was achieved by using a reverse phase C18 coloum (Hypersil BDS 250X 4.6X5µm). The mobile phase composed methanol : phosphate buffer in ratio 70:30 at flow rate of 1ml/min .The ph was adjusted to 4.5 with .1N NaOH. Detection was carried out using a UV-vis detector at 215 nm. The mean retention time of duloxetine hydrochloride (DUL)and methylcobalamin(MCB) was found to be 3.3 min 6.7 min respectively. The method was found to be linear in the range of 30 - 90 µg/ml and 2.5-6.75 µg/ml for DUL and MCB respectively, with mean recovery of 98.88 % DUL and 100.22% for MCB the correlation coefficient for both DUL and MCB were closed to one. The developed method was validated according to ICH guidelines and values of accuracy, precision and other statistical analysis were found to be in good accordance with the prescribe values thus proposed method was successfully applied for simultaneous determination of DUL and MCB in routine analysis of formulation.