Background: Graviola, is commonly known as soursop. The leaves of this tropical fruit tree are traditionally used for its various medicinal benefits. The present study aims at estimating the anti-inflammatory and antioxidant activity ofgraviolaleaf extract against nephrotoxicity caused by lead acetate in albino rats. Methods: Forty rats were divided into four groups, (group I) control, (group II) graviola leaves extract 100 mg/kg BW, (group III) lead acetate 400 mg/kg BW and (group IV) lead acetate plus graviola leaves extract. After 8 weeks Blood and kidney tissue samples were collected for estimation biochemical, oxidative and inflammatory parameters in addition   to histo-pathological examination. Results:  The lead acetate induced rats exhibited significant elevations in kidney function parameters (urea, creatinine, uric acid, cystatin A and LDH), pro-inflammatory markers (IL-6 and Pentraxin-3) and, markers of oxidative stress (MDA and 8-OHdG) and  a significantly decrease in the activities of antioxidant enzymes (CAT, SOD, GR, GPx and GST) and reduced GSH. On the other hand, graviola leaves extract was significantly effective in lowering kidney dysfunction parameters, pro inflammatory markers and oxidative stress markers and significantly elevated the activity of the antioxidant parameters. Additionally, treatment with graviola leaves extract improved the histopathological abnormalities occurred in nephrotoxicity. Conclusion: Our results provide an evidence of the benefit of using graviola leaves as a potent antioxidant and anti-inflammatory plant for treatment of nephrotoxicity induced by lead acetate.