This study assessed the anti-oxidative potentials of ethanol seed extract of Cola lepidota in High Fat Fed (HFD) female Wistar Albino rats. Thirty (30) apparently healthy female albino wistar rats weighing between 80 – 90g were divided into five (5) equal groups for the study which lasted for 90 days. Group I which served as negative control was fed with 200g of normal rat chow and water daily. Group II which served as positive control received 200g of high fat diet (HFD) daily. Group III received 200g of HFD for the first 30 days and 200g of HFD + 300mg/kg of extract for the remaining 60 days. Group IV received 200g of HFD for the first 30 days and 200g of HFD + 300mg/kg of ascorbic acid for the remaining 60 days. Group V received 200g of HFD for the first 30 days and 200g of HFD + 300mg/kg of extract + 300mg/kg of ascorbic acid for the remaining 60 days. All administrations were done orally; standard analytical methods were used for the determination of serum superoxide dismutase (SOD) activity, serum malondialdehyde (MDA) level, serum catalase activity and whole blood glutathione (GSH) level. The result indicated a significant reduction in the concentration of all the antioxidants in the HFD untreated group (group II) compared to other groups with the concentrations of SOD, CAT and GSH in group II being......