Stem cells play a critical role in the regulation of growth and development of multicellular species. In rice, the shoot growing zone comprises a small population of stem cells, self-renewing cells which can differentiate into diverse specialized organs and tissues such as stems, leaves and flowers. Drought effects on rice have been studied extensively, however, the effect of water deficit on the development of rice growing zone cells which are protected by the surrounding mature leaf tissue, has not been explored. Two rice cultivars with contrasting genetic backgrounds and levels of tolerance to drought, Nipponbare and IAC1131, were used in this study. Four-week-old seedlings of both cultivars were grown in large soil volumes and then exposed to moderate and extreme drought for 7 days, followed by 3 days of re-watering. Shoot growing zone tissues were harvested from plants from each treatment for protein extraction and subsequent shotgun proteomic analysis. Gene Ontology (GO) annotations of differentially expressed proteins provide insights into different developmental processes of Nipponbare and IAC1131. Our data indicate that IAC1131 appears to be better able to cope with stressful conditions by up regulating a suite of proteins potentially involved in cell division, developmental process, cellular component organization and cell growth, to maintain the active state of the growing zone. Nipponbare, on the contrary, lacks the range of stress responses shown by the drought tolerant variety, and the cell division activity is severely impaired by drought stress.