Objective: Thiazolidinediones, acting as peroxisome proliferator-activated receptor gamma (PPARγ) ligands, has been reported to reduce hepatic steatosis in human and animals. However, the underlying mechanism remains largely unknown. The purpose of this study was to investigate changes in oxylipins (oxygenated fatty acid derivatives) and underlying mechanism by treatment with lobeglitazone (LOBE), a PPARγ ligand in an animal model of obesity and type 2 diabetes. Methods: Male obese and diabetic OLETF rats were orally administered either vehicle (CONTROL) or LOBE (1mg/kg) fed on high fat/ high carbohydrate diet for 15 weeks. Blood and liver tissue were harvested after overnight fasting at the end of study. Biochemical and histological assessment were performed in plasma and liver. Oxylipins in plasma and liver were analyzed via metabolomic analyses. For in vitro study, oxylipins were treated on HepG2 human hepatoma cell line and THP-1 human monocyte cell line. Results: OLETF rats that received LOBE showed decreased in hepatic fat accumulation in liver and improvement of lipid profiles in liver and plasma including total cholesterol, triglyceride and free fatty acid compared to CONTROL rats. LOBE treatment significantly altered levels of oxylipins including resolvins, specialized pro-resolving mediators derived from essential fatty acids, in the plasma and liver. Among the oxylipins we identified, resolvins showed improvement in hepatic fat accumulation and inflammation in HepG2 and THP-1 cells. Conclusion: Our results demonstrate that LOBE can regulate oxylipin metabolism including resolvins in a rat model of obesity and type 2 diabetes, which could contribute to the improvement of hepatic steatosis and inflammation.