Background：Lead (Pb), a naturally occurring environmental contaminant, has been implicated in several pathological conditions of the cardiovascular and renal systems.Objective：The study was designed to evaluate the modulatory roles of the polyphenol-rich fraction of Terminalia catappa on chronic lead acetate-induced cardiovascular and renal toxicities in rats.Methods：Thirty-six rats were randomly selected and divided into six groups of six rats each. Pb toxicity was induced by the administration of 100 mg/L Pb in drinking water for 12 weeks in groups B-F. Groups A and B were left untreated; groups C and D were treated with polyphenol-rich fraction of Terminalia catappa [PRFTC (100 and 200 mg/kg b.w.)]; vitamin E (50 mg/kg b.w.) and lisinopril (10 mg/kg b.w.) were administered to groups E and F, respectively.Results：Exposure of rats to Pb induced significantly elevated (P < 0.05) primary haemodynamic parameters, severe disseminated congestion of blood vessels and haemorrhages in the cardiac and renal tissues, significantly elevated (P < 0.05) markers of oxidative stress markers of inflammation and myocardial infarction, but significantly decreased serum nitric oxide and the systemic antioxidants. Furthermore, rats exposed to Pb showed heightened immune-positive reactions to Caspase-3, a marker of apoptosis, in both renal and cardiac tissues. All manifestations of Pb-associated toxicities in the cardiovascular and renal systems were alleviated by the PRFTC treatment in rats.Conclusion：The polyphenol-rich fraction of T. catappa proved effective in the reduction of oxidative stress-mediated derangements of the physiological homeostasis and decreased apoptosis in the cardiovascular and renal systems of rats chronically exposed to lead acetate toxicities and may therefore have therapeutic potential as a supplement that can be applied in chronic lead poisoning.