The physiological, biochemical, and proteomic changes in germinating rice seedlings were investigated under arsenic stress. A marked decrease in germination percentage, shoot, and root elongation as well as plant biomass was observed with arsenic treatments, as compared to control, whereas accumulation of arsenic and malondialdehyde (MDA) in seedlings were increased significantly with increasing arsenic concentration (both AsIII and AsV). The up-regulation of some antioxidant enzyme activities and the isozymes of superoxide dismutase (SOD, EC 1.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), peroxidase (POD, EC 1.11.1.7), and glutathione reductase (GR, 1.6.4.2) substantiated that arsenic accumulation generated oxidative stress, which was more pronounced in As(III) treatment. We also studied the protective effect of reduced glutathione (GSH) and cysteine (Cys) to As(III)/As(V) stressed seedlings. Both GSH and Cys imparted enhanced tolerance to seedlings against arsenic stress. Seedlings growth improved while level of MDA declined significantly when GSH and Cys were supplemented to As(III)/As(V) treatments suggesting GSH and Cys-mediated protection against oxidative stress. The arsenic content was highest in roots of seedlings grown in As(III) in the presence of GSH/Cys. However, in case of As(V) plus GSH or Cys, the arsenic content in seedlings was highest in shoots. The results are suggestive of differential metabolism of As(III) and As(V) in rice.