Background: Obesity is a disorder involving excessive fat accumulation which increases the formation of reactive oxygen species that leads to inflammation and atherosclerosis. Perilla (Perilla frutescens) leaves possess anti-inflammatory effects and is rich in antioxidants, such as terpenoid, carotenoid, phenol, and flavonoid. The purpose of this study was to prove whether the administration of perilla (Perilla frutescens) leaves extract may have an inhibitory effect towards the build-up of TNF-alpha, IL-6, and foam cell in obese Wistar rats. Methods: This research was an experimental randomized post-test only control group design. Samples were 34 obese male rats (Rattus norvegicus) aged 6-8 weeks. The samples were divided into 2 groups, namely the control group which was obese rats administered with high fat diet and placebo (distilled water), and the treatment group which was obese rats allotted with high fat diet and perilla (Perilla frutescens) leaves extract with a dose of 500 mg/kg rat weight for 4 weeks. TNF-alpha and IL-6 were measured by ELISA method from rat blood serum, foam cell was examined by histopathology examination from the ascending aorta. The research data was analyzed using T-independent test. Results: The results showed that there was a significantly lower outcome in the mean level of TNF-alpha, the mean of control group was 80.09±1.64 pg/mL and the treatment group was 60.40±1.35 pg/mL (p<0.001). Similarly, there was a significantly lower results in the mean level of IL-6, the mean of control group was 0.67±0.00 pg/mL and the treatment group was 0.51±0.08 pg/mL (p<0.05). There was no significant difference in the mean level of foam cell, the p value was 0.215 even though the mean level of foam cell in control group was 1.78±2.60 cells/field of view and in treatment group was 0.70±1.72 cells/field of view. Conclusions: From the outcomes of this study, it could be concluded that oral administration of perilla (Perilla frutescens) leaves extract significantly inhibited the increase of TNF alpha levels and IL-6 levels, but did not inhibit the increase of foam cell amount in obese Wistar rat.