Here we study the simplicity of an iterated Ore extension of a unital ring [Formula: see text]. We give necessary conditions for the simplicity of an iterated Ore extension when [Formula: see text] is a commutative domain. A class of iterated Ore extensions, namely the differential polynomial ring [Formula: see text] in [Formula: see text]-variables is considered. The conditions for a commutative domain [Formula: see text] of characteristic zero to be a maximal commutative subring of its differential polynomial ring [Formula: see text] are given, and the necessary and sufficient conditions for [Formula: see text] to be simple are also found.