Aims Early studies have identified type 1 diabetes mellitus (T1DM) as a disease that is caused by the autoimmune destruction of the insulin-producing pancreatic beta-cells. Genetics, environment and the immune pathogenesis of T1DM are three major pillars of T1DM research. We try to understand the changes in the gene expression profile during the pathogenesis of T1DM. Methods We performed a systematic search in the Gene Expression Omnibus (GEO) database for microarray studies of T1DM with samples taken at or before the T1DM onset. Results The results of an integrated analysis of different GEO datasets and a comparison of the gene expression level in T1DM samples taken at the time of appearance of the islet autoantibodies, 1 year before T1DM onset, and at the time of T1DM onset showed that CD274, which encodes PD-L1, was up-regulated in the newly onset T1DM samples. CD274 had a stable expression level in the control samples but showed a gradual up-regulation from the appearance of autoantibodies to the onset of T1DM. Conclusions These results indicate that CD274 up-regulation in T1DM is correlated with disease pathogenesis. PD-L1 might play a protective role in preventing the pancreatic islets from autoimmune destruction, which may help researchers find strategies for preventing the destruction process of pancreas beta-cells in T1DM.