Although studies have shown that grain-filling and programmed cell death of wheat endosperm are affected by drought stress, which is closely related to ethylene and abscisic acid.The mechanism of ethylene and abscisic acid regulate grain-filling and endosperm PCD under drought stress is remains unclear. In this study, we regulated the production of ethylene and abscisic acid in wheat grains under drought stress at filling stage by chemicals. The results showed that spraying ethylene synthesis inhibitor enhanced endosperm cell viability, delayed nuclear deformation, and decreased ACC content. Compared with the CK, the CN significantly decreased the DNA hydrolase activity and significantly increased the DNA content. In addition, the CN treatment reduced the expression of four genes related to ethylene receptors (ers1, ers2 etr1, etr2) and increase the expression of dad1. Under CN treatment, the process of endosperm PCD was delayed, the duration of high grouting rate was prolonged, and the grain weight was increased, in contrast, the opposite result was obtained after spraying abscisic acid synthesis inhibitor. The production of abscisic acid and ethylene in grains determines the fate of endosperm cells. A new model of artificial regulation of abscisic acid and ethylene, delaying endosperm PCD process and increasing grain weight under post-anthesis drought was proposed.