Prostate gland represents one of the main parts of male reproductive system. The influence of diabetes and or hypercholesterolemia on prostate damage is still not clear. In this experiment, forty male Wistar albino rats weighing approximately 100 g were arranged into four groups: control, diabetic (single i.p. 40 mg streptozotocin/kg B.wt) and hypercholesterolemic (diet supplement 3% cholesterol) and combined treatment. Treatment was carried out for 12 weeks. At the end of treatment, animals were sacrificed and prostate and thyroid gland were separated and processed for histological investigations, assessment of biochemical markers of vascular endothelial growth factors (VEGF), heat shock protein 70 (HSP-70),  8-hydroxy-deoxyguanosine (8-HDG), adhesive molecules ((ICAM-1 and VCAM-1) as well as quantitative and qualitative isoenzyme electrophoresis of  malate dehydrogenase (MDH), lactic dehydrogenase (LDH), Aspartate aminotransferase(AST) and glucose-6 phosphate dehydrogenase (G6PDH). Comet assay for prostate was also determined. The present findings reported increased histopathological alterations in thyroid and prostate glands coincides with increased prostate levels of HSP 70, 8-HDG and activity of LDH, MDH and G6-PDH in comparison with the control. However, there was a marked depletion of prostate contents of VEGF, adhesive molecules (V-CAM, I-CAM) as well as the enzyme activity of AST. The assayed isoenzymes were markedly altered in diabetic and or hypercholesterolemic reflecting altered prostate function. These findings were parallel with increased DNA damage. It was concluded that diabetes and or hypercholesterolemia led to marked alteration of thyroid gland and interfered in prostate gland function as assessed by biochemical markers, comet assay and isoenzyme electrophoresis.