OBJECTIVE: The aim of the study was to assess the possible protective role of grape seeds extract (GSE) in ameliorating the toxic effects of paracetamol overdose on the rat renal cortical tissue. BACKGROUND: Paracetamol is one of the widely used non-steroidal anti-infl ammatory drugs (NSAIDs). Unfortunately, it was reported as the most common cause of toxic ingestion in the world. Grape seeds extract (GSE) is known to have a strong antioxidant and anti-infl ammatory properties. METHODS: The rats were divided into 4 groups; control group, GSE group, paracetamol group and GSE with paracetamol group. Kidney specimens were processed for biochemical, histological and immunohisto-chemical studies. RESULTS: The study showed marked biological changes in the form of signifi cant increase in serum urea and creatinine levels with signifi cant decrease in renal superoxide dismutase with paracetamol group. Furthermore, Proximal (PCT) and distal convoluted tubules showed marked degeneration, dense nuclear staining, cytoplasmic vacuolization, and partial loss of the brush borders. Most tubules were dilated, irregular and were fi lled with hyaline casts. PCT and DCT showed less PAS reaction and more COX-2 and caspase expression if compared with the control and the GSE groups. Concomitant administration of grape seeds extract with paracetamol revealed a noticeable amelioration of these biochemical and histological changes. Proximal and distal convoluted tubules showed less PAS reaction and more COX 2 and caspase expression if compared with the control and the GSE. Concomitant administration of GSE with paracetamol revealed a noticeable amelioration of these biochemical and histological changes. CONCLUSION: Grape seeds extract provided biochemical and histo-pathological improvement in paracetamol induced renal cortical toxicity. These fi ndings revealed that this improvement was associated with a decrease in oxidative damage and apoptosis (Tab. 1, Fig. 7, Ref. 55). Text in PDF www.elis.sk. KEY WORDS: grape seeds extract, paracetamol, renal cortex and superoxide dismutase.