Water status is the main factor affecting rice production. In order to understand rice strategies in response to drought condition in the field, the drought-responsive mechanisms at the physiological and molecular levels were studied in two rice genotypes with contrasting susceptibility to drought stress at reproductive stage. After 20 d of drought treatment, the osmotic potential of leaves reduced 78% and 8% in drought susceptible rice cultivar Zhenshan97B and tolerant rice cultivar IRAT109, respectively. The panicle lengths had no obvious changes in drought stressed Zhenshan97B and IRAT109, suggesting that drought stress impose less effect on assimilate translocation from leaf to vegetative growth of panicles. IRAT109 showed more extensive deeper root growth that could be considered a second line of defense against drought stress. The C_i/C_a ratio exhibited enhancement over reduction of g_s in both cultivars, reflecting the non-stomatal limitation to photosynthesis occurred during drought stress. Orthophosphate dikinase, glycine dehydrogenase, ribulose bisphosphate carboxylase (Rubisco), glycine hydroxymethyltransferase and ATP synthase were down-regulated for Zhenshan97B in response to drought stress, suggesting the reduction of capacity of carbon assimilation in this rice cultivar. In drought-stressed IRAT109, transketolase, Rubisco were down-regulated, however, Rubisco activase and peptidyl-prolyl cis–trans isomerase, which might alleviate the damage on Rubisco by drought stress, were up-regulated. The increased abundances of chloroplastic superoxide dismutase [Cu–Zn] and dehydroascorbate reductase might provide antioxidant protection for IRAT109 against damage by dehydration.