Computation approach to identify significance of proteins related with disease was proposed as one of the solutions from the problem of experimental method application which is generally high cost and time consuming. The case of study was conducted on Diabetes Melitus (DM) type 2 diseases. Identification of significant proteins was conducted by constructing protein-protein interactions network and then analyzing the network topology. Dataset was obtained from Online Mendelian Inheritance in Man (OMIM) and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) which provided protein data related with a disease and Protein-Protein Interaction (PPI), respectively. The results of topology analysis towards Protein-Protein Interaction (PPI) showed that there were 21 significant protein associated with DM where INS as a network center protein and AKTI, TCF7L2, KCNJ11, PPARG, GCG, INSR, IAPP, SOCS3 were proteins that had close relation directly with INS.