Abstract: The effects of pink guava (Psidium guajava) puree on enzyme activities and histology on High Fat Diet (HFD)-induced obese rats were investigated. Thirty male Sprague-Dawley rats were divided into Control Negative (CN) fed with rat pellet; control positive, low, medium and high dose group (CP, LDG, MDG and HDG) were fed HFD-AIN93G, respectively. CN and CP were given distilled water; meanwhile treated group were given the aqueous puree, at concentration of 500, 1000 and 2000 mg/kg body weight, dissolved in distilled water were administered orally via a drinking bottle, respectively. Pink guava puree was supplemented with the HFD diet for six weeks. The rats were fasted overnight and euthanized under an anesthetic condition with ethyl ether and blood was collected from the posterior vena cava at the end of experiment. A significant reduction in body weight was observed in the treated groups as compared to CN and CP group. Specific activities of Glutathione Peroxidase (GPx), Glutathione Reductase (GR) and Superoxide Dismutase (SOD) of the HFD-induced obese rats were significantly increased in comparison with the CN group. Histologically, the liver and kidney cells in LDG, MDG and HDG showed no significant differences as compared to CN and CP’s liver and kidney cells. Treatment with low, medium and high doses showed improved features in HFD induced-obese rat’s liver and kidney cells. In conclusion, pink guava puree due to its antioxidant role was helpful in protecting organ tissues in experimental animals and has a significant impact on specific activities of HFD induced-obese rats.