This study describes the development and characterization of Enteric coated pellets of duloxetine hydrochloride that results to improve gastric stability and enhance oral systemic exposure of novel serotonin and nor-epinephrine reuptake inhibitor (SNRI), duloxetine. Duloxetine Pellets were prepared by coating drug solution on sugar sphere followed by various layering in fluidized bed Coater (FBC) with different polymers like hydroxy propyl methylcellulose (HPMC E5), Crospovidone, Hypermellose Acetate Succinate and polysorbate 80 in suitable proportion. In vitro Dissolution studies were carried out in 0.1N HCl (pH: 2) for two hours followed by Phosphate buffer (pH: 6.8) for 1.5 hours with USP (Type-II) dissolution method. Absorption studies for Optimized pellets were carried out in Rats at 5 mg/kg dose; pellets were filled in Capsule size 9 administered orally with modified gavage needle. The optimized formulation has better correlation in both In vitro and In vivo system. The systemic exposure (AUC) and maximum concentration in plasma (Cmax) of entiric coated pellets of duloxetine was significantly higher than conventional suspension formulation. Finally it can be concluded that multiparticulate approach can be used to improve the stability and systemic exposure of pH sensitive and poorly water-soluble drugs such as duloxetine.