The pancreas is an organ composed of (98%) exocrine and (2%) endocrine cells. Diabetes mellitus is a disease characterized by derangement in carbohydrate, protein, and fat metabolism caused by the complete or relative insufficiency of insulin secretions and or insulin action. Two major types of diabetes, one associated with insulin deficiency called Type-1 or insulin-dependent diabetes mellitus (IDDM) and the other associated with insulin resistance called Type-2 or noninsulin-dependent diabetes mellitus (NIDDM). Models for IDDM explains chemically induced diabetes, hormone-induced diabetes mellitus, insulin antibodies-induced diabetes, diabetes induced by viral agents, and surgically induced diabetes. Genetic models are discussed. Models for NIDDM discuss neonatal STZ model of NIDDM (chemically induced diabetes) and other chemically induced NIDDM models. Genetic models of NIDDM are explained. Normoglycemic animal models are discussed. In vitro methods on isolated organs, cells and membranes are described. The in vitro perfusion of isolated pancreas helps to study the effect of the drug on insulin, glucagon, and somatostatin secretion without interference from other organ changes. Muscle cell lines are discussed. In vitro assays for insulin or insulin-like substances on adipocytes are explained. The uptake of (3H) glucose into fat cells and incorporation of this radiolabelled glucose in the lipids can measure insulin or insulin-like activity. Assays for lipid synthesis in isolated adipocytes are described. In vitro assays of glucose transport in adipocytes, and glucose uptake by the isolated diaphragm from mice and rats are discussed. Glycogen synthase activity is studied. Insulin receptor-binding assays are described.