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Temidayo S Omolaoye,1,2 Shantal Lynn Windvogel,1,3 Stefan S Du Plessis1,2 1Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa; 2Department of Basic Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates; 3Centre for Cardio-Metabolic Research in Africa, Stellenbosch University, Cape Town, South AfricaCorrespondence: Stefan S Du PlessisDepartment of Basic Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, P.O. Box 505055, Dubai, 505055, United Arab EmiratesEmail Stefan.duplessis@mbru.ac.aeBackground: Testicular insulin signalling is altered in diabetic (DM) males. While unravelling the mechanism through which DM exert these detrimental effects, studies have shown the importance of insulin regulation in glucose homeostasis, and how a lack in insulin secretion indirectly led to reduced male fertility. The current study aimed to investigate the role of rooibos, honeybush and Sutherlandia on insulin signalling in the testicular tissue of type I diabetic rats.Methods: Animals (n=60) were randomly divided into six groups. The groups include a control group, a vehicle group, and diabetes was induced in the remainder of animals via a single intraperitoneal injection of STZ at 45mg/kg. The remaining four groups included a diabetic control (DC), diabetic + rooibos (DRF), diabetic + honeybush (DHB) and diabetic + Sutherlandia group (DSL). Animals were sacrificed after seven weeks of treatment, and blood and testes were collected.Results: All diabetic groups (DC, DRF, DHB, DSL) presented with a significant increase in blood glucose levels after diabetes induction compared to the control and vehicle (p< 0.001). The DC animals presented with decreased testicular protein expression of IRS-1, PkB/Akt and GLUT4 compared to controls. DRF and DHB animals displayed an acute upregulation in IRS-1, whil