Background Grape seeds are considered a raw material with high content of phytochemicals that can be used as a source of dietary supplements with antioxidative properties. grape seeds has showed considerable anti-diabetic activity by inhibiting the activities of amylase and α-glucosidase, improving the function and structure of the pancreas and Langerhans islets and alleviating insulin resistance. Moreover, grape can prevent the development of diabetic complications, such as diabetic nephropathy and diabetic retinopathy Several studies have investigated the role of inflammatory markers (cytokines and chemokines) in diabetes development and its complications. Aim: In this study we aimed to evaluation the possible beneficial effects of grape seed proanthocyanidens extract on the renal damage cause by type-2 diabetes mellitus in the terms of renal inflammatory cytokines and serum cystatin-C associated with induced hyperglycemia in male rats by (HFHCD+STZ-induced T2DM rat model. We targeted the determination the cytokines activity IL-6 and IL-10 in Kidney tissues Lysate and the renal function damage golden marker serum cystatin-C so the traditional function markers were done moreover The hepatic , pancreatic and renal histopathological examinations were performed to evaluate the therapeutic potentials of GSPE on the induced metabolic complications caused by T2DM on the kidney, liver and pancreatic tissues of the HFHCD+STZ-induced T2DM male albino rats model.The progression of T2DM can be slowed or even reversed by making lifestyle changes, such as losing weight, eating a healthy diet, and exercising regularly. However, for many people, medication is also necessary to control Hyperglycaemia. Methods: the experiment, the rats were divided into two main groups including SNC group (standard negative control )/ 8 rats) and HFHCD group (High fate High cholesterol Diet)/ 32 rats) which later divided into 4 groups (positive control ( diabetes ) – orally administrated groups with 200 mg CγWWLSP , 400 mg and 5 mg decalazide ) .