Diabetes mellitus (DM) and its complications impose a significant burden on patients and the health care system. In the Traditional Persian Medicine (TPM), barley is recommended for treatment of DM. This study sought to assess the effect of barley seed aqueous extract on hepatic, pancreatic, renal and cardiac tissues in normal (non-diabetic) and Streptozotocin-induced diabetic rats. Twenty-one male Wistar rats were randomly divided into diabetic and non-diabetic groups. Diabetes was induced by single intraperitoneal injection of Streptozotocin. After one week, the diabetic and non-diabetic groups were randomly divided into control and barley seed extract subgroups namely N group (non-diabetic control rats), S group (seed extract treated non-diabetic rats), D group (diabetic control rats) and DS group (seed extract treated diabetic rats). After 6 weeks, all rats were sacrificed for histopathological analysis and specimens were stained routinely for histological studies. The abnormal histological signs significantly decreased in the DS group compared to D group. Also, protective effects of barley seed extract against histopathological changes were seen in S group compared to N group.These findings suggest that barley seed extract exerts a protective effect on different tissues in diabetes.