Paraquat (PQ) is a highly toxic quaternary nitrogen herbicide capable of increasing superoxide anion production. The present study was carried out to evaluate the oxidative damage induced by PQ in rat kidney and its effect on antioxidant defense system and nephrotoxicity biomarkers in addition to the role of proanthocyanidin in alleviating its toxic effects. Male Wister albino rats were randomly divided into four groups of 10 each, group I served as control; group II treated with proanthocyanidin (25 mg/kg BW), group III received single dose of paraquat (PQ; 10 mg/kg BW; i.p) and group IV treated with both PQ and proanthocyanidin. Rats were orally administered their respective doses of proanthocyanidine daily for 21 days. The local committee approved the design of the experiments, and the protocol conforms to the guidelines of the National Institutes of Health (NIH). The administration of PQ caused significant elevation in lipid peroxidation (LPO) and reduction in the activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). A significant reduction in glutathione (GSH) content was also observed. Serum urea, creatinin and lactate dehydrogenase (LDH) activity were significantly increased. Histopathological manifestations were investigated in tissues from rat kidney. As expected, PQ administration induced marked changes in the morphological structure of the kidney in PQ demonstrated animals since necrotic changes in both glomeruli and renal tubules were observed. Proanthocyanidin treatment to PQ treated rats decreased LPO level and normalized SOD, CAT and GST activities, while GSH content was increased. Also, urea, creatinin and LDH were maintained near normal level due to proanthocyanidine treatment. In addition, proanthocyanidin attenuated the morphological damages induced by PQ in the kidney tissue of experimental animals. Our results suggest antitoxic and antioxidant effects of proanthocyanidin against paraquat.