The aim of present research was to develop piperine loaded chitosan microspheres to evaluate enhanced hepatoprotective activity in paracetamol induced hepatotoxic mice model. Piperine was extracted from Pippali Piper Longum. Solvent evaporation method was employed to fabricate the microspheres. Optical microscopy demonstrated that the formulation was spherical and had smooth texture with no drug crystals or microsphere aggregation. Formulations containing 2 mg piperine were administered orally to the animal model. In paracetamol induced hepatotoxic mice model, SGOT and SGPT level demonstrated no significant elevation in the blood by the microspheres formulation. The histopathology and enzyme level results suggested that microsphere formulation can passively target hepatoprotective drug to the liver.