Experimental evidence from previous study has demonstrated the hypolipidemic effects of Oryctes rhinoceros oil (ORO) when fed as a supplement to a cholesterol-based diet. Due to renew interest in the consumption of insect derived oil, the present study was designed to elucidate the effect of Oryctes rhinoceros oil (ORO) supplementation in comparison to vitamin E on oxidative status in some tissues of rats fed a cholesterol-based diet. Forty (40) Swiss albino rats were divided into 4 groups (n = 10) and maintained on a basal diet (cholesterol free as control), a cholesterol-based diet (5% cholesterol as cholesterol), a cholesterol-based diet supplemented with ORO (cholesterol + ORO) and a cholesterol-based diet supplemented with vitamin E (Cholesterol + vit E) for 10 weeks. Animals in the cholesterol group had a significantly (p <0.05) higher malondialdehyde (MDA), conjugated diene and nitric oxide concentrations in the serum, liver, heart, kidney and lung compared to control, cholesterol + ORO and cholesterol + vit E groups. Tissue glutathione (GSH) concentration was significantly (p <0.05) higher in rats fed cholesterol-based diet supplemented with ORO and vitamin E compared to those fed cholesterol-based diet alone. Xanthine oxidase activity was significantly (p <0.05) reduced in tissues of rats fed ORO and vitamin E supplemented diets compared to cholesterol rat group. In addition, catalase and superoxide dismutase activities in the various tissues examined were significantly (p <0.05) higher in both ORO and vitamin E supplemented groups compared to the cholesterol group. No significant difference was observed between animals fed ORO and vitamin E supplemented diets. These results showed that Oryctes rhinoceros larva oil exhibited similar protective effects to vitamin E against diet-induced oxidative stress in rats. In addition, data from this study showed that Oryctes rhinoceros larva oil possessed antioxidant property. Overall, the potential nutritional benefit of Oryctes rhincoceros larva oil consumption on cardiovascular health could possibly involve its ability to upregulation of cellular antioxidant defense mechanisms.