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Introduction: Multiple studies have shown strong relationships between different nutrients in plants, and the important role of N in Zn acquisition and translocation has been recognized., Objectives: The aim of this study was to estimate the effect of Zn on N uptake, translocation, and distribution in rice as well as the corresponding molecular mechanisms. We also aimed to evaluate the impact of N on the Zn content in rice grains which is closely related to the Zn nutrition in humans with rice-based diets., Methods: We conducted both field trials and hydroponic cultures of two rice cultivars to analyze the growth and yield, the uptake, translocation, and distribution of N and Zn, as well as the expression of N transport and assimilation genes, and the Zn transporter genes under different combined applications of N and Zn., Results: Zn supply promoted the root-to-shoot translocation (12-70% increasing) and distribution of N into the leaves (19-49% increasing) and brown rice (6-9% increasing) and increased the rice biomass (by 14-35%) and yield (by 13-63%). Zn supply induced the expression of OsNRTs and OsAMTs in both roots and shoots, but repressed the expression of OsNiR2 , OsGS1;2 , and OsFd-GOGAT in roots, whereas it activated the expression of OsNiR 2, OsGS1;1 , OsGS2 , and OsFd-GOGAT in the shoots. Moreover, the enzyme activities of nitrite reductase, nitrate reductase, and glutamine synthetase increased and the free NO 3 - concentration decreased, but the soluble protein concentration increased significantly in the shoots after Zn supply. Synergistically, N significantly facilitated the root-to-shoot translocation (1.68-11.66 fold) and distribution of Zn into the leaves (1.68-6.37 fold) and brown rice (7-12% increasing) and upregulated the expression levels of Zn transporter genes in both the roots and shoots., Conclusions: We propose a working model of the cross-talk between Zn and N in rice plants, which will aid in the appropriate combined application of Zn and N fertilizers in the field to improve both N utilization in plants and Zn nutrition in humans with rice-based diets., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University.)