The present study evaluated the anti-obesity properties of papaya in high-fat (HF) diet fed rats. In the portion of the present study, the effects of papaya juice on pancreatic lipase enzyme activity was assessed, and it was shown that papaya exhibited an inhibitory effect on these enzymes. In the portion of the study, papaya was found to reduce the expression levels of markers of obesity, inflammation and oxidative stress in rats. Obesity was induced in 28 male Sprague Dawley rats by feeding them a HF diet for 12 weeks. The anti-obesity effects of papaya was evaluated by feeding papaya juice orally in with two experimental doses: 0.5 ml (HFL) and 1.0 ml (HFH) per 100 g of body weight. The HF diet resulted in significant increases in the body weight, serum triglyceride, serum total cholesterol and serum low-density lipoprotein cholesterol levels, as well as a decrease in serum high-density lipoprotein cholesterol levels. The HF diet also induced adipocyte hypertrophy, lipid accumulation and increased malondialdehyde levels. Papaya reversed all of these changes and significantly increased serum superoxide dismutase and decreased serum cytokine (interleukin-6) levels. The protein expression of levels PPARγ in the HF group was significantly increased compared with the other groups, but was decreased significantly in the HFH group. Histological observations of epididymal adipose tissue provided evidence for the lipid-lowering effects of papaya. The results of the present study demonstrate that papaya has the potential to reduce the risk of obesity associated with adiposity, anti-inflammation and anti-oxidation.