The D-instanton partition function is a fascinating quantity because in the presence of N D3-branes, and in a certain decoupling limit, it reduces to the functional integral of = 4 U(N) supersymmetric gauge theory for multi-instanton solutions. We study this quantity as a function of non-commutativity in the D3-brane theory, VEVs corresponding to separating the D3-branes and α'. Explicit calculations are presented in the one-instanton sector with arbitrary N, and in the large-N limit for all instanton charge. We find that for general instanton charge, the matrix theory admits a nilpotent fermionic symmetry and that the action is -exact. Consequently the partition function localizes on the minima of the matrix theory action. This allows us to prove some general properties of these integrals. In the non-commutative theory, the contributions come from the ``Higgs Branch'' and are equal to the Gauss-Bonnet-Chern integral of the resolved instanton moduli space. Separating the D3-branes leads to additional localizations on products of abelian instanton moduli spaces. In the commutative theory, there are additional contributions from the ``Coulomb Branch'' associated to the small instanton singularities of the instanton moduli space. We also argue that both non-commutativity and α'-corrections play a similar rôle in suppressing the contributions from these singularities. Finally we elucidate the relation between the partition function and the Euler characteristic of the instanton moduli space.
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