Abstract: Endoplasmic reticulum (ER) stress is a type of cellular adaptive reaction to ischemia, hypoxia and hyperglycemia and has three pathways, namely, PKR-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE-1α) and activating transcription factor 6 (ATF6). Strong ER stress will induce cellular apoptosis through CHOP, JNK and caspase pathways, which may stimulate myocardial interstitial fibroblast and result in myocardial remodeling and collagen deposition. In recent years, many studies show that diabetes mellitus (DM) myocardial fibrosis has a close relation to ER stress and a better understanding of the mechanism between them is important for the development of new drugs for DM myocardial fibrosis. In this article we will introduce the mechanism and pathways of ER stress and the mechanism of DM myocardial fibrosis and look into the possible relation between the two.