In this study, T2DM rats were utilized to determine the levels of the 78 kDa glucose-regulated protein (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), inositol requiring enzyme 1α/β (IRE1), ionized calcium-binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and tight junction protein 1 or zonula occludens-1 (ZO-1) (by RT-PCR and western blot analysis) and assess their distribution in VMH immunohistochemically after metformin and PA treatment and their combined action. Here, ERN1 is linked to type 2 diabetes mellitus.