Objective: Lobeglitazone, a potent thiazolidinedione (TZD)-based activator of peroxisome proliferator-activated receptor gamma (PPARr), has been approved for the treatment of type 2 diabetes mellitus in Korea. We aimed to investigate the effects of lobeglitazone on adipose tissue (AT) and liver stetosis, as well as the metabolic phenotypes in db/db mice. Methods: Seven-week-old male db/db mice were randomly assigned to two groups with (1) vehicle-treated (N = 8), and (2) lobeglitazone-treated groups (N = 8). Lobeglitazone (1 mg/kg) was intraperitoneally injected daily for 20 weeks. Epididymal, subcutaneous, brown AT, and livers were harvested for histological, immunohistochemical, and gene expression analyses. The expressions of marker genes for M1 and M2 macrophages from mouse epididymal AT were analyzed using flow cytometry. Metabolic activity of brown AT was assessed by positron emission tomography-computed tomography (PET-CT). Results: Lobeglitazone treatment of 20 weeks increased the body weight by 15% than vehicle group (P = 0.002). While the mean random glucose level at 20 weeks was 416.5 mg/dL in the vehicle group, lobeglitazone treatment significantly lowered it from 1 week after treatment and decreased it further by the mean value of 72.0 mg/dL at 20 weeks. Whereas epididymal AT mass was significantly decreased (P = 0.012), subcutaneous AT was increased in lobeglitazonetreated group. The CD11c-positive M1 macrophages and CD206-positive M2 macrophages in the epididymal fat tissue exhibited decreased M1-to-M2 ratio by lobeglitazone treatment. Furthermore, in lobeglitazone-treated group, interscapular brown AT mass was significantly increased (P < 0.001), and it also clearly visualized by PET-CT compared to vehicle group. Liver weight (P = 0.015) and hepatic triglyceride contents (P = 0.007) were significantly decreased in lobeglitazone-treated mice. Lobeglitazone treatment also significantly increased phosphorylation of hepatic AMPK and ACC, and decreased circulating levels of free fatty acids, showing increased fatty acid oxidation. Conclusion: These findings point towards a beneficial role for lobeglitazone treatment for 20 weeks in AT and liver steastosis as well as improvement in metabolic phenotype.