Dimethyl sulfoxide (DMSO) is the key reagent to dissolve starch in the starch structural analysis. In this paper, solubility and structural changes of corn starch in DMSO/water system were studied. Corn starch achieved maximum solubility of 97.15% in 90% DMSO solution when the dissolution time reaches 12 h. With the excessive dissolution, no significant change in solubility was detected. Scanning electron microscopy (SEM) analysis showed that starch granules structure were the largest damaged in 90% DMSO, which confirmed that 90% DMSO was the best solvent for starch. High performance size exclusion chromatography (HPSEC) and high performance anion-exchange chromatography (HPAEC) found that the molecular weight and radius of gyration of starch dissolved in 90% DMSO gradually decreased with the extension of the dissolution time, which indicated that starch molecules were degraded. Furthermore, theB₂ and B₃ chains of amylopectin were more easily to degrade, and the B₁ chains were relatively stable.