Methods and compositions are provided for modulating pancreatic islet β cell proliferation. Aspects of the methods include promoting β cell proliferation by providing agents that promote PDGFR signaling, or inhibiting β cell proliferation by providing agents that inhibit PDGFR signaling. These methods find a number of uses, including, for example, in the treatment of diabetes and human islet diseases. Also provided are reagents and kits thereof that find use in practicing the subject methods.