Methods for treating type two diabetes mellitus in a subject in need thereof and pharmaceutical compositions for the treatment of type two diabetes mellitus are disclosed. The methods include administering an effective amount of apolipoprotein A-IV to the subject. The pharmaceutical composition includes apolipoprotein A-IV formulated for administration to a subject for the treatment of type two diabetes mellitus. Also disclosed are methods for substantially restoring glucose tolerance in a subject in need thereof to a normal level and methods for lowering blood glucose levels in a subject in need thereof.