Increased evidence in role of oxidative stress and grape seed extract (GSE) in diabetes and its complication led us to investigate the changes of oxidative stress and anti-oxidant defence in liver tissue of diabetic rats and possible effects of GSE. Diabetes was induced by a single intraperitoneal injection of streptozotocin. Seven days after STZ injection four groups were formed: Control, GSE-supplemented control, diabetic and GSE-supplemented diabetic and GSE was given for 6 weeks. Malondialdehyde levels and xanthine oxidase activities were not different among the groups. However, nitric oxide (NO) levels were higher in diabetic and GSE supplemented groups compared with non-diabetic and non-supplemented groups, respectively. Total anti-oxidant activity (TAA) was lower in diabetic groups compared with their non-diabetic controls and it was not affected by GSE. In conclusion, GSE supplementation has limited protective effect in liver tissue of diabetic rats via affecting NO levels and was not affecting TAA. © 2012 Informa UK, Ltd.