The fibroblast growth factor family plays numerous roles in controlling and determining functions of some hormonal appropriate tissues o-r organs. Numerous studies have focused on the part of FGF21 in metabolic ubiquitin lysine regulation in the liver, fat, and even skeletal muscle. Nevertheless, the role of FGF21 in other organs has not been well resolved. The expression of FGF21 mRNA was located in the testis, but what exactly is the biological function of FGF21 in-the testis remains unclear. In-fact, it has been appreciated that the other FGF family members such as FGF1, 2, 4, 8, and 9 are also indicated in the male reproductive system and are intimately involved in tes ticular maturation, Sertoli cell proliferation and differentiation, some members of FGF family such as FGF4 play impor-tant anti apoptotic role in the protection of the testicular cells against the harmful effect. Testicular apoptotic cell death does occur in many conditions, including the normal spermatogenesis and also serious diseases such as diabetes. We’ve shown Mitochondrion that diabetes causes testicular apoptotic cell death predominantly through mitochondrial and endoplasmic reticulum stress associated cell death pathways, which may be metabolic abnormality induced oxidative damage. Whether FGF21 being an important metabolic mediator can also be involved in the preservation of-the spermatogenesis and whether FGF21 protects the germ cells from diabetes induced apoptotic cell death have never been examined. Allegedly FGF21 increases the survival-of pancreatic ep cells. INS 1E cells and islets isolated from FGF21 treated diabetic subjects were somewhat protected from sugar, lipid, and cytokine induced apoptosis. Additionally, the safety of FGF21 from oxidized low-density lipoprotein induced apoptotic buy Canagliflozin cell death was also seen in cardiac microvascular endothelial cells. Thus, the current study aimed to test our theory the testicular FGF21 term is necessary for the conventional spermatogenesis and in a position to protect the germ cells from diabetes induced apoptotic cell death. To these ends, we have examined the mRNA expression of FGF21 in the testis of fasting and non fasting mice or mice with typ-e 1 diabetes. The typ-e 1 diabetes mouse model was stimulated with streptozotocin. We also examined the result of Fgf21 gene deletion on the testicular apoptotic cell death spon taneously or induced by type 1 diabetes with Fgf21 gene knock-out mice and wild type mice were matched by their age. In-addition, we also formulated exogenous FGF21 to FGF21 KO dia betic rats to immediately establish the anti apoptotic effect of FGF21 o-n diabetes induced testicular cell death. FGF21 KO mice with C57BL/6J history were given as a gift from Dr. Steve Kliewer, University of Texas Southwestern Medical Center. Age matched WT settings were obtained from Jackson Laboratory.