The goal of present study is to evaluate and recognize the most effective hepatoprotective solvent fractions of methanolic extract of Paeonia emodi by fractionating and assessing its fractions for hepatoprotective effect in paracetamol-induced liver damage in mice. In this study, some liver-related serum parameters such as AST, ALP, and ALT were studied. Maximum reduction was caused by aqueous extract (61.08 %) followed by a butanol extract (60.26 %), chloroform extract (48.76 %), crude extract (45.48 %) and drug (37.93 %), in case of ALT. During the study of AST, chloroform extract caused a maximum reduction (65.94 %), followed by a butanol extract (60.43 %), aqueous extract (57.13 %), crude extract (57.13 %) and drug (43.94 %). During the study of ALP aqueous fraction caused a maximum reduction (47.22 %), followed by a butanol fraction (44.44 %), chloroform (41.51 %), methanol extract (34.72 %) and drug (20.83 %). In all the treatment groups the serum levels of ALT, AST and ALP were significantly lower as compared to those of untreated controlled group (P<0.05). The present research showed that Paeonia emodi has the potential to reduce paracetamol-induced hepatotoxicity in mice and restore the normal liver function.