Utilizing the Molecular Electron Density Theory, to survey the [2+3] cycloaddition processes between 4-methyl-Benzonitrile-N-oxide (1) and 9α-hydroxyparthenolide (2), reaction, activation energies and the reactivity indices are determined. An examination of conceptual DFT indices, 9α-hydroxyparthenolide (2) will provide in this reaction as an eletrophile, whereas 4-methyl-Benzonitrile-N-oxide (1) will share as a nucleophile. The reaction and activation energies clearly demonstrate that this cyclization is regio- chemo and stereospecific, which is in perfect agreement with the outcomes of the experiment. The mechanism of this [2+3] cycloaddition follows two steps mechanism, as indicated by ELF analysis.