Pathological remodelling of adipose tissue in obesity; including the occurrence of enlarged adipocyte, is often as a result of leptin insensitivity, the mechanism of which is still poorly understood. Leptin is produced in proportion to fat mass to increase energy expenditure. However, the enlarged adipocyte displays an altered metabolic capacity and gene expression profile despite the elevated circulating leptin levels. We have studied the adipose tissue remodelling in Zucker (fa/fa) rats, proposed to be the most appropriate rodent model for the early onset of human obesity, due to a mutation in the long form of the leptin receptor. We determined the effects of obesity, exercise and/or psychological stress on visceral adipose tissue (VAT) phenotype in Zucker rats. Lean (LZR) and obese (OZR) Zucker rats (male, 8-9 weeks old, n=64) were divided into (1) Controls, (2) unpredictable chronic mild stress (UCMS), (3) treadmill exercise (Ex), or (4) UCMS+Ex, 8 rats per strain in each experimental group for 8 weeks (Brooks et al., 2018). VAT was sectioned and stained with haematoxylin and eosin (H&E) staining. Total RNA was extracted with TRIzol reagent as described (Toni et al., 2018). Values are means ± S.E.M., compared by ANOVA. To determine the adipose tissue phenotype, tissue cellularity and gene expression profile in VAT were analysed. Analysis of tissue cellularity using H&E staining showed that obesity increased adipocyte size in the VAT of the OZR compared with LZR (7728±286.7, 3089±160.3µm2; p< 0.001; n≥4). Neither exercise and/or psychological stress had any effect on the tissue cellularity. Leptin mRNA was quantified using quantitative polymerase chain reaction (qPCR). One of the features of OZR is the elevated circulating leptin levels compared with LZR. Contrary to the increased adipocyte size in OZR, obesity caused downregulation of leptin mRNA in OZR compared with LZR (1.2±0.2, 4.8±1.1; p<0.05; n≥6). To further elucidate our findings, the mRNA of peroxisome proliferator-activated receptor-γ (PPAR-γ) was quantified using qPCR method. PPAR-γ is a transcription factor that positively regulate adipocyte differentiation and lipid storage. The data showed that obesity downregulated PPAR-γ mRNA when compared OZR to LZR (0.8±0.1, 1.8±0.3; p<0.05, n≥6). However, the interventions of exercise, and/or psychological stress did not affect the mRNA of leptin and PPAR-γ. Our study demonstrates that obesity increases adipocyte size but downregulated the gene expression of leptin. We demonstrate the impaired regulation of adipocyte differentiation in visceral adipose tissue of OZR group. However, exercise and/or psychological stress had no effect on tissue cellularity and, gene expression in both LZR and OZR. Further studies are needed to establish the extent to which leptin signalling links VAT to the development of metabolic and cardiovascular diseases.