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The purpose of this study was to assess the possible protective role of exogenous salicylic acid (SA), sodium nitroprusside (SNP), a donor of nitric oxide, and their combination on 21-day-old safflower (Carthamus tinctorius L.) seedlings grown under zinc (Zn) stress. The results revealed that exposure to 500 µM ZnSO 4 .7H 2 O for 10 days markedly reduced the root and shoot dry weights in Zn-treated plants, while the application of SA, SNP and specially SA + SNP significantly increased the root and shoot dry weights in seedlings subjected to Zn stress. Addition of SA, SNP and SA + SNP interestingly reduced root-to-shoot translocation of zinc and increased significantly the level of glutathione (GSH) and ascorbate (ASC) in leaves of Zn-stressed plants. The Zn-treated plants supplemented with SA and SNP revealed an improved activity of ascorbate-glutathione cycle enzymes and those enzymes which are involved in glyoxalase system as compared to the plants treated with Zn only. However, no significant relationship was found between SA or SNP supplementation and glutathione S-transferase activity in Zn-stressed plants. These findings demonstrate that exogenous application of SA or SNP could ameliorate the negative effects of Zn on safflower plants probably by stimulation of antioxidant defense and glyoxalase systems.