Backround Both type 2 diabetes (T2D) and Alzheimer's disease affect large number of people all over the world, especially in developed countries, and involve common molecular mechanisms in degenerative processes. Aim Our study is to investigate the expression levels of the ADAMTS4, TIMP3, RELN, and BCAN genes which encode extracellular matrix molecules and are thought to be related to the pathophysiology of Alzheimer's disease in rats that we used to develop a T2D model by injection of a streptozotocin (STZ) and feeding with high-fat diet (HFD). Material and methods In total, 40 rats were divided into four groups: HFD + STZ (10), HFD (10), STZ (10), and the control (10). The weight and blood glucose levels of all rats were recorded, and the insulin tolerance test was performed. At the end of the experimental period, the hippocampus of the rats was isolated and a part of this was used for gene expression analysis through real-time PCR, whereas other parts were used for histological analyses. Results Our results show that plaque-like structures were found in the histological examination of the experimental T2D model. In molecular studies, the expression levels of the ADAMTS4, TIMP3, RELN, and BCAN genes were decreased in the HFD +STZ and STZ groups compared with the control, whereas the same expression levels, except that of inhibitor TIMP3, were found to increase in the HFD group. Conclusion These genes encoding proteases that regulate neuronal activity have decreased levels in the T2D model. There may be potential in the adoption of new treatment approaches for Alzheimer's and T2D.