GPR120/FFAR4 has been recognized as a functional fatty acid receptor and an attractive therapeutic target for metabolic diseases. Previously, we have demonstrated that GPR120/FFAR4 deficit (GPR120KO) mice facilitate an inflammatory response of the nonalcoholic fatty liver diseases (NAFLD) after short-term a 0.1% methionine and choline deficient high-fat (CDAHF) feeding compared to WT mice. In this study, we investigated whether GPR120KO mice after long-term CDAHF feedings induce the progression of nonalcoholic steatohepatitis (NASH). Mice fed with CDAHF diet for 6 weeks showed a significant increase in plasma aspartate transaminase and alanine transaminase levels, fatty deposition, inflammatory cell infiltration, and sever fibrosis. Both WT mice and GPR120KO mice fed CDAHF diet showed increment of the number of crown like structures and the immunoreactivity for F4/80 positive cells. However, GPR120KO mice significantly increased TGF-b mRNA collagen type 1 α mRNA in the liver compared to WT mice fed CDAHF diet, indicating that GPR120KO mice fed CDAHF diet showed more severe liver fibrosis than that of WT mice fed CDAHF diet. Therefore, our findings suggest that GPR120 signaling could be helpful as a regulatory factor of NAFLD/NASH progression.